1t5x - Revision history

OCA at 06:26, 23 August 2023

OCA — Wed, 23 Aug 2023 06:26:18 GMT

←Older revision		Revision as of 06:26, 23 August 2023
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	<StructureSection load='1t5x' size='340' side='right'caption='[[1t5x]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='1t5x' size='340' side='right'caption='[[1t5x]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1t5x]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/~~"micrococcus_aureus"_(rosenbach_1884)_zopf_1885 "micrococcus aureus" (rosenbach 1884) zopf 1885~~] and [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T5X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1T5X FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1t5x]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens], [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C] and [https://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T5X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1T5X FirstGlance]. <br>
-	</td></tr><tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat"~~><div style='overflow: auto; max-height: 3em;'>[[1aqd\|1aqd]], [[1dlh\|1dlh]], [[1klu\|1klu]], [[1pyw\|1pyw]], [[1t5w\|1t5w]]</div></td></tr>~~	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2.5Å</td></tr>
-	~~<tr~~ id~~='gene'><td class~~="~~sblockLbl~~">~~<b>~~[[~~Gene~~\|~~Gene:~~]]~~</b></td><td class="sblockDat">HLA-DRA0101 ([https://www~~.~~ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=~~5&id=9606 HUMAN]), HLA-DRB10101 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), SEC3 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1280 "Micrococcus aureus" (Rosenbach 1884) Zopf 1885])</td></tr>	+
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1t5x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t5x OCA], [https://pdbe.org/1t5x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1t5x RCSB], [https://www.ebi.ac.uk/pdbsum/1t5x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1t5x ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1t5x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t5x OCA], [https://pdbe.org/1t5x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1t5x RCSB], [https://www.ebi.ac.uk/pdbsum/1t5x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1t5x ProSAT]</span></td></tr>
	</table>		</table>
-	== Disease ==
-	[[https://www.uniprot.org/uniprot/2B11_HUMAN 2B11_HUMAN]] Genetic variation in HLA-DRB1 is a cause of susceptibility to sarcoidosis type 1 (SS1) [MIM:[https://omim.org/entry/181000 181000]]. Sarcoidosis is an idiopathic, systemic, inflammatory disease characterized by the formation of immune granulomas in involved organs. Granulomas predominantly invade the lungs and the lymphatic system, but also skin, liver, spleen, eyes and other organs may be involved.<ref>PMID:14508706</ref>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/ENTC3_STAAU ENTC3_STAAU]] Staphylococcal enterotoxins cause the intoxication staphylococcal food poisoning syndrome. The illness is characterized by high fever, hypotension, diarrhea, shock, and in some cases death. [[https://www.uniprot.org/uniprot/DRA_HUMAN DRA_HUMAN]] Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells. The peptide binding cleft accommodates peptides of 10-30 residues. The peptides presented by MHC class II molecules are generated mostly by degradation of proteins that access the endocytic route, where they are processed by lysosomal proteases and other hydrolases. Exogenous antigens that have been endocytosed by the APC are thus readily available for presentation via MHC II molecules, and for this reason this antigen presentation pathway is usually referred to as exogenous. As membrane proteins on their way to degradation in lysosomes as part of their normal turn-over are also contained in the endosomal/lysosomal compartments, exogenous antigens must compete with those derived from endogenous components. Autophagy is also a source of endogenous peptides, autophagosomes constitutively fuse with MHC class II loading compartments. In addition to APCs, other cells of the gastrointestinal tract, such as epithelial cells, express MHC class II molecules and CD74 and act as APCs, which is an unusual trait of the GI tract. To produce a MHC class II molecule that presents an antigen, three MHC class II molecules (heterodimers of an alpha and a beta chain) associate with a CD74 trimer in the ER to form a heterononamer. Soon after the entry of this complex into the endosomal/lysosomal system where antigen processing occurs, CD74 undergoes a sequential degradation by various proteases, including CTSS and CTSL, leaving a small fragment termed CLIP (class-II-associated invariant chain peptide). The removal of CLIP is facilitated by HLA-DM via direct binding to the alpha-beta-CLIP complex so that CLIP is released. HLA-DM stabilizes MHC class II molecules until primary high affinity antigenic peptides are bound. The MHC II molecule bound to a peptide is then transported to the cell membrane surface. In B-cells, the interaction between HLA-DM and MHC class II molecules is regulated by HLA-DO. Primary dendritic cells (DCs) also to express HLA-DO. Lysosomal miroenvironment has been implicated in the regulation of antigen loading into MHC II molecules, increased acidification produces increased proteolysis and efficient peptide loading. [[https://www.uniprot.org/uniprot/MIG1_YEAST MIG1_YEAST]] Involved in glucose repression of the SUC, GAL and MAL genes as well as of the CAT8 gene. Binds to two sites in the upstream region of SUC2. [[https://www.uniprot.org/uniprot/2B11_HUMAN 2B11_HUMAN]] Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells. The peptide binding cleft accommodates peptides of 10-30 residues. The peptides presented by MHC class II molecules are generated mostly by degradation of proteins that access the endocytic route; where they are processed by lysosomal proteases and other hydrolases. Exogenous antigens that have been endocytosed by the APC are thus readily available for presentation via MHC II molecules; and for this reason this antigen presentation pathway is usually referred to as exogenous. As membrane proteins on their way to degradation in lysosomes as part of their normal turn-over are also contained in the endosomal/lysosomal compartments; exogenous antigens must compete with those derived from endogenous components. Autophagy is also a source of endogenous peptides; autophagosomes constitutively fuse with MHC class II loading compartments. In addition to APCs; other cells of the gastrointestinal tract; such as epithelial cells; express MHC class II molecules and CD74 and act as APCs; which is an unusual trait of the GI tract. To produce a MHC class II molecule that presents an antigen; three MHC class II molecules (heterodimers of an alpha and a beta chain) associate with a CD74 trimer in the ER to form a heterononamer. Soon after the entry of this complex into the endosomal/lysosomal system where antigen processing occurs; CD74 undergoes a sequential degradation by various proteases; including CTSS and CTSL; leaving a small fragment termed CLIP (class-II-associated invariant chain peptide). The removal of CLIP is facilitated by HLA-DM via direct binding to the alpha-beta-CLIP complex so that CLIP is released. HLA-DM stabilizes MHC class II molecules until primary high affinity antigenic peptides are bound. The MHC II molecule bound to a peptide is then transported to the cell membrane surface. In B-cells; the interaction between HLA-DM and MHC class II molecules is regulated by HLA-DO. Primary dendritic cells (DCs) also to express HLA-DO. Lysosomal miroenvironment has been implicated in the regulation of antigen loading into MHC II molecules; increased acidification produces increased proteolysis and efficient peptide loading.	+	[https://www.uniprot.org/uniprot/DRA_HUMAN DRA_HUMAN] Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells. The peptide binding cleft accommodates peptides of 10-30 residues. The peptides presented by MHC class II molecules are generated mostly by degradation of proteins that access the endocytic route, where they are processed by lysosomal proteases and other hydrolases. Exogenous antigens that have been endocytosed by the APC are thus readily available for presentation via MHC II molecules, and for this reason this antigen presentation pathway is usually referred to as exogenous. As membrane proteins on their way to degradation in lysosomes as part of their normal turn-over are also contained in the endosomal/lysosomal compartments, exogenous antigens must compete with those derived from endogenous components. Autophagy is also a source of endogenous peptides, autophagosomes constitutively fuse with MHC class II loading compartments. In addition to APCs, other cells of the gastrointestinal tract, such as epithelial cells, express MHC class II molecules and CD74 and act as APCs, which is an unusual trait of the GI tract. To produce a MHC class II molecule that presents an antigen, three MHC class II molecules (heterodimers of an alpha and a beta chain) associate with a CD74 trimer in the ER to form a heterononamer. Soon after the entry of this complex into the endosomal/lysosomal system where antigen processing occurs, CD74 undergoes a sequential degradation by various proteases, including CTSS and CTSL, leaving a small fragment termed CLIP (class-II-associated invariant chain peptide). The removal of CLIP is facilitated by HLA-DM via direct binding to the alpha-beta-CLIP complex so that CLIP is released. HLA-DM stabilizes MHC class II molecules until primary high affinity antigenic peptides are bound. The MHC II molecule bound to a peptide is then transported to the cell membrane surface. In B-cells, the interaction between HLA-DM and MHC class II molecules is regulated by HLA-DO. Primary dendritic cells (DCs) also to express HLA-DO. Lysosomal miroenvironment has been implicated in the regulation of antigen loading into MHC II molecules, increased acidification produces increased proteolysis and efficient peptide loading.
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
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	==See Also==		==See Also==
	*[[MHC 3D structures\|MHC 3D structures]]		*[[MHC 3D structures\|MHC 3D structures]]
		+	*[[MHC II 3D structures\|MHC II 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Anderson, M W~~]]	+	[[Category: Saccharomyces cerevisiae S288C]]
-	[[Category: ~~Gorski, J~~]]	+	[[Category: Staphylococcus aureus]]
-	[[Category: ~~Stern, L J~~]]	+	[[Category: Anderson MW]]
-	[[Category: ~~Strug, I~~]]	+	[[Category: Gorski J]]
-	[[Category: ~~Zavala-Ruiz, Z~~]]	+	[[Category: Stern LJ]]
-	[[Category: ~~Antigen~~]]	+	[[Category: Strug I]]
-	[[Category: ~~Hla~~-~~dr1]]~~	+	[[Category: Zavala-Ruiz Z]]
-	~~[[Category: Immune system]]~~	+
-	~~[[Category: Major histocompatibiloty complex protein]]~~	+
-	~~[[Category: Mhc class ii]]~~	+
-	~~[[Category: Peptide]]~~	+
-	~~[[Category: Superantigen~~]]	+

OCA at 15:38, 27 October 2021

OCA — Wed, 27 Oct 2021 15:38:45 GMT

OCA at 11:43, 24 December 2020

OCA — Thu, 24 Dec 2020 11:43:13 GMT

←Older revision		Revision as of 11:43, 24 December 2020
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	==HLA-DR1 in complex with a synthetic peptide (AAYSDQATPLLLSPR) and the superantigen SEC3-3B2==		==HLA-DR1 in complex with a synthetic peptide (AAYSDQATPLLLSPR) and the superantigen SEC3-3B2==
-	<StructureSection load='1t5x' size='340' side='right' caption='[[1t5x]], [[Resolution\|resolution]] 2.50Å' scene=''>	+	<StructureSection load='1t5x' size='340' side='right'caption='[[1t5x]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1t5x]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/"micrococcus_aureus"_(rosenbach_1884)_zopf_1885 "micrococcus aureus" (rosenbach 1884) zopf 1885] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T5X OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=1T5X FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1t5x]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/"micrococcus_aureus"_(rosenbach_1884)_zopf_1885 "micrococcus aureus" (rosenbach 1884) zopf 1885] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T5X OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1T5X FirstGlance]. <br>
-	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1aqd\|1aqd]], [[1dlh\|1dlh]], [[1klu\|1klu]], [[1pyw\|1pyw]], [[1t5w\|1t5w]]</td></tr>	+	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1aqd\|1aqd]], [[1dlh\|1dlh]], [[1klu\|1klu]], [[1pyw\|1pyw]], [[1t5w\|1t5w]]</div></td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HLA-DRA0101 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), HLA-DRB10101 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), SEC3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1280 "Micrococcus aureus" (Rosenbach 1884) Zopf 1885])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HLA-DRA0101 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), HLA-DRB10101 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), SEC3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1280 "Micrococcus aureus" (Rosenbach 1884) Zopf 1885])</td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=1t5x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t5x OCA], [http://pdbe.org/1t5x PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1t5x RCSB], [http://www.ebi.ac.uk/pdbsum/1t5x PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1t5x ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1t5x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t5x OCA], [http://pdbe.org/1t5x PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1t5x RCSB], [http://www.ebi.ac.uk/pdbsum/1t5x PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1t5x ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
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	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/t5/1t5x_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/t5/1t5x_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
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	</div>		</div>
	<div class="pdbe-citations 1t5x" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 1t5x" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[MHC 3D structures\|MHC 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
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	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Anderson, M W]]		[[Category: Anderson, M W]]
	[[Category: Gorski, J]]		[[Category: Gorski, J]]

OCA at 14:03, 12 October 2017

OCA — Thu, 12 Oct 2017 14:03:32 GMT

←Older revision		Revision as of 14:03, 12 October 2017
Line 1:		Line 1:
		+
	==HLA-DR1 in complex with a synthetic peptide (AAYSDQATPLLLSPR) and the superantigen SEC3-3B2==		==HLA-DR1 in complex with a synthetic peptide (AAYSDQATPLLLSPR) and the superantigen SEC3-3B2==
	<StructureSection load='1t5x' size='340' side='right' caption='[[1t5x]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='1t5x' size='340' side='right' caption='[[1t5x]], [[Resolution\|resolution]] 2.50Å' scene=''>
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	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1aqd\|1aqd]], [[1dlh\|1dlh]], [[1klu\|1klu]], [[1pyw\|1pyw]], [[1t5w\|1t5w]]</td></tr>		</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1aqd\|1aqd]], [[1dlh\|1dlh]], [[1klu\|1klu]], [[1pyw\|1pyw]], [[1t5w\|1t5w]]</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HLA-DRA0101 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), HLA-DRB10101 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), SEC3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1280 "Micrococcus aureus" (Rosenbach 1884) Zopf 1885])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HLA-DRA0101 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), HLA-DRB10101 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), SEC3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1280 "Micrococcus aureus" (Rosenbach 1884) Zopf 1885])</td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1t5x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t5x OCA], [http://pdbe.org/1t5x PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1t5x RCSB], [http://www.ebi.ac.uk/pdbsum/1t5x PDBsum]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1t5x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t5x OCA], [http://pdbe.org/1t5x PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1t5x RCSB], [http://www.ebi.ac.uk/pdbsum/1t5x PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1t5x ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
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	</div>		</div>
	<div class="pdbe-citations 1t5x" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 1t5x" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[Major histocompatibility complex\|Major histocompatibility complex]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 06:27, 8 February 2016

OCA — Mon, 08 Feb 2016 06:27:48 GMT

←Older revision		Revision as of 06:27, 8 February 2016
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	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</jmolCheckbox>
-	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/~~chain_selection~~.php?pdb_ID=~~2ata~~ ConSurf].	+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1t5x ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">

OCA at 08:48, 10 September 2015

OCA — Thu, 10 Sep 2015 08:48:06 GMT

←Older revision		Revision as of 08:48, 10 September 2015
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	<StructureSection load='1t5x' size='340' side='right' caption='[[1t5x]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='1t5x' size='340' side='right' caption='[[1t5x]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1t5x]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~] and [http://en.wikipedia.org/wiki/~~Staphylococcus_aureus Staphylococcus aureus~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T5X OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1T5X FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1t5x]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/"micrococcus_aureus"_(rosenbach_1884)_zopf_1885 "micrococcus aureus" (rosenbach 1884) zopf 1885] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T5X OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1T5X FirstGlance]. <br>
	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1aqd\|1aqd]], [[1dlh\|1dlh]], [[1klu\|1klu]], [[1pyw\|1pyw]], [[1t5w\|1t5w]]</td></tr>		</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1aqd\|1aqd]], [[1dlh\|1dlh]], [[1klu\|1klu]], [[1pyw\|1pyw]], [[1t5w\|1t5w]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HLA-DRA0101 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~]), HLA-DRB10101 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~]), SEC3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1280 ~~Staphylococcus~~ aureus])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HLA-DRA0101 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), HLA-DRB10101 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), SEC3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1280 "Micrococcus aureus" (Rosenbach 1884) Zopf 1885])</td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1t5x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t5x OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1t5x RCSB], [http://www.ebi.ac.uk/pdbsum/1t5x PDBsum]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1t5x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t5x OCA], [http://pdbe.org/1t5x PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1t5x RCSB], [http://www.ebi.ac.uk/pdbsum/1t5x PDBsum]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 29:		Line 29:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 1t5x" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 36:		Line 37:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens]]~~	+	[[Category: Human]]
-	~~[[Category: Staphylococcus aureus~~]]	+
	[[Category: Anderson, M W]]		[[Category: Anderson, M W]]
	[[Category: Gorski, J]]		[[Category: Gorski, J]]

OCA at 07:18, 6 January 2015

OCA — Tue, 06 Jan 2015 07:18:56 GMT

←Older revision		Revision as of 07:18, 6 January 2015
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1t5x]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T5X OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1T5X FirstGlance]. <br>		<table><tr><td colspan='2'>[[1t5x]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T5X OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1T5X FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1aqd\|1aqd]], [[1dlh\|1dlh]], [[1klu\|1klu]], [[1pyw\|1pyw]], [[1t5w\|1t5w]]</td></tr>	+	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1aqd\|1aqd]], [[1dlh\|1dlh]], [[1klu\|1klu]], [[1pyw\|1pyw]], [[1t5w\|1t5w]]</td></tr>
-	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HLA-DRA0101 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), HLA-DRB10101 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), SEC3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1280 Staphylococcus aureus])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HLA-DRA0101 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), HLA-DRB10101 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), SEC3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1280 Staphylococcus aureus])</td></tr>
-	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1t5x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t5x OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1t5x RCSB], [http://www.ebi.ac.uk/pdbsum/1t5x PDBsum]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1t5x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t5x OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1t5x RCSB], [http://www.ebi.ac.uk/pdbsum/1t5x PDBsum]</span></td></tr>
-	<table>	+	</table>
	== Disease ==		== Disease ==
	[[http://www.uniprot.org/uniprot/2B11_HUMAN 2B11_HUMAN]] Genetic variation in HLA-DRB1 is a cause of susceptibility to sarcoidosis type 1 (SS1) [MIM:[http://omim.org/entry/181000 181000]]. Sarcoidosis is an idiopathic, systemic, inflammatory disease characterized by the formation of immune granulomas in involved organs. Granulomas predominantly invade the lungs and the lymphatic system, but also skin, liver, spleen, eyes and other organs may be involved.<ref>PMID:14508706</ref>		[[http://www.uniprot.org/uniprot/2B11_HUMAN 2B11_HUMAN]] Genetic variation in HLA-DRB1 is a cause of susceptibility to sarcoidosis type 1 (SS1) [MIM:[http://omim.org/entry/181000 181000]]. Sarcoidosis is an idiopathic, systemic, inflammatory disease characterized by the formation of immune granulomas in involved organs. Granulomas predominantly invade the lungs and the lymphatic system, but also skin, liver, spleen, eyes and other organs may be involved.<ref>PMID:14508706</ref>
Line 38:		Line 38:
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Staphylococcus aureus]]		[[Category: Staphylococcus aureus]]
-	[[Category: Anderson, M W.]]	+	[[Category: Anderson, M W]]
-	[[Category: Gorski, J.]]	+	[[Category: Gorski, J]]
-	[[Category: Stern, L J.]]	+	[[Category: Stern, L J]]
-	[[Category: Strug, I.]]	+	[[Category: Strug, I]]
-	[[Category: Zavala-Ruiz, Z.]]	+	[[Category: Zavala-Ruiz, Z]]
	[[Category: Antigen]]		[[Category: Antigen]]
	[[Category: Hla-dr1]]		[[Category: Hla-dr1]]

OCA at 21:34, 29 September 2014

OCA — Mon, 29 Sep 2014 21:34:16 GMT

←Older revision		Revision as of 21:34, 29 September 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_1t5x~~\| ~~PDB~~=1t5x \| ~~SCENE~~= }}	+	==HLA-DR1 in complex with a synthetic peptide (AAYSDQATPLLLSPR) and the superantigen SEC3-3B2==
-	===HLA-~~DR1~~ in complex with a ~~synthetic~~ peptide (~~AAYSDQATPLLLSPR~~) and the ~~superantigen SEC3~~-~~3B2~~===	+	<StructureSection load='1t5x' size='340' side='right' caption='[[1t5x]], [[Resolution\|resolution]] 2.50Å' scene=''>
-	~~{{ABSTRACT_PUBMED_15489166}}~~	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[1t5x]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T5X OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1T5X FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1aqd\|1aqd]], [[1dlh\|1dlh]], [[1klu\|1klu]], [[1pyw\|1pyw]], [[1t5w\|1t5w]]</td></tr>
		+	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HLA-DRA0101 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), HLA-DRB10101 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), SEC3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1280 Staphylococcus aureus])</td></tr>
		+	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1t5x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t5x OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1t5x RCSB], [http://www.ebi.ac.uk/pdbsum/1t5x PDBsum]</span></td></tr>
		+	<table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/2B11_HUMAN 2B11_HUMAN]] Genetic variation in HLA-DRB1 is a cause of susceptibility to sarcoidosis type 1 (SS1) [MIM:[http://omim.org/entry/181000 181000]]. Sarcoidosis is an idiopathic, systemic, inflammatory disease characterized by the formation of immune granulomas in involved organs. Granulomas predominantly invade the lungs and the lymphatic system, but also skin, liver, spleen, eyes and other organs may be involved.<ref>PMID:14508706</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/ENTC3_STAAU ENTC3_STAAU]] Staphylococcal enterotoxins cause the intoxication staphylococcal food poisoning syndrome. The illness is characterized by high fever, hypotension, diarrhea, shock, and in some cases death. [[http://www.uniprot.org/uniprot/DRA_HUMAN DRA_HUMAN]] Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells. The peptide binding cleft accommodates peptides of 10-30 residues. The peptides presented by MHC class II molecules are generated mostly by degradation of proteins that access the endocytic route, where they are processed by lysosomal proteases and other hydrolases. Exogenous antigens that have been endocytosed by the APC are thus readily available for presentation via MHC II molecules, and for this reason this antigen presentation pathway is usually referred to as exogenous. As membrane proteins on their way to degradation in lysosomes as part of their normal turn-over are also contained in the endosomal/lysosomal compartments, exogenous antigens must compete with those derived from endogenous components. Autophagy is also a source of endogenous peptides, autophagosomes constitutively fuse with MHC class II loading compartments. In addition to APCs, other cells of the gastrointestinal tract, such as epithelial cells, express MHC class II molecules and CD74 and act as APCs, which is an unusual trait of the GI tract. To produce a MHC class II molecule that presents an antigen, three MHC class II molecules (heterodimers of an alpha and a beta chain) associate with a CD74 trimer in the ER to form a heterononamer. Soon after the entry of this complex into the endosomal/lysosomal system where antigen processing occurs, CD74 undergoes a sequential degradation by various proteases, including CTSS and CTSL, leaving a small fragment termed CLIP (class-II-associated invariant chain peptide). The removal of CLIP is facilitated by HLA-DM via direct binding to the alpha-beta-CLIP complex so that CLIP is released. HLA-DM stabilizes MHC class II molecules until primary high affinity antigenic peptides are bound. The MHC II molecule bound to a peptide is then transported to the cell membrane surface. In B-cells, the interaction between HLA-DM and MHC class II molecules is regulated by HLA-DO. Primary dendritic cells (DCs) also to express HLA-DO. Lysosomal miroenvironment has been implicated in the regulation of antigen loading into MHC II molecules, increased acidification produces increased proteolysis and efficient peptide loading. [[http://www.uniprot.org/uniprot/MIG1_YEAST MIG1_YEAST]] Involved in glucose repression of the SUC, GAL and MAL genes as well as of the CAT8 gene. Binds to two sites in the upstream region of SUC2. [[http://www.uniprot.org/uniprot/2B11_HUMAN 2B11_HUMAN]] Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells. The peptide binding cleft accommodates peptides of 10-30 residues. The peptides presented by MHC class II molecules are generated mostly by degradation of proteins that access the endocytic route; where they are processed by lysosomal proteases and other hydrolases. Exogenous antigens that have been endocytosed by the APC are thus readily available for presentation via MHC II molecules; and for this reason this antigen presentation pathway is usually referred to as exogenous. As membrane proteins on their way to degradation in lysosomes as part of their normal turn-over are also contained in the endosomal/lysosomal compartments; exogenous antigens must compete with those derived from endogenous components. Autophagy is also a source of endogenous peptides; autophagosomes constitutively fuse with MHC class II loading compartments. In addition to APCs; other cells of the gastrointestinal tract; such as epithelial cells; express MHC class II molecules and CD74 and act as APCs; which is an unusual trait of the GI tract. To produce a MHC class II molecule that presents an antigen; three MHC class II molecules (heterodimers of an alpha and a beta chain) associate with a CD74 trimer in the ER to form a heterononamer. Soon after the entry of this complex into the endosomal/lysosomal system where antigen processing occurs; CD74 undergoes a sequential degradation by various proteases; including CTSS and CTSL; leaving a small fragment termed CLIP (class-II-associated invariant chain peptide). The removal of CLIP is facilitated by HLA-DM via direct binding to the alpha-beta-CLIP complex so that CLIP is released. HLA-DM stabilizes MHC class II molecules until primary high affinity antigenic peptides are bound. The MHC II molecule bound to a peptide is then transported to the cell membrane surface. In B-cells; the interaction between HLA-DM and MHC class II molecules is regulated by HLA-DO. Primary dendritic cells (DCs) also to express HLA-DO. Lysosomal miroenvironment has been implicated in the regulation of antigen loading into MHC II molecules; increased acidification produces increased proteolysis and efficient peptide loading.
		+	== Evolutionary Conservation ==
		+	[[Image:Consurf_key_small.gif\|200px\|right]]
		+	Check<jmol>
		+	<jmolCheckbox>
		+	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/t5/1t5x_consurf.spt"</scriptWhenChecked>
		+	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
		+	<text>to colour the structure by Evolutionary Conservation</text>
		+	</jmolCheckbox>
		+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
		+	<div style="clear:both"></div>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Peptides bind to class II major histocompatibility complex (MHC) proteins in an extended conformation. Pockets in the peptide binding site spaced to accommodate peptide side chains at the P1, P4, P6, and P9 positions have been previously characterized and help to explain the obtained peptide binding specificity. However, two peptides differing only at P10 have significantly different binding affinities for HLA-DR1. The structure of HLA-DR1 in complex with the tighter binding peptide shows that the peptide binds in the usual polyproline type II conformation, but with the P10 residue accommodated in a shallow pocket at the end of the binding groove. HLA-DR1 variants with polymorphic residues at these positions were produced and found to exhibit different side chain specificity at the P10 position. These results define a new specificity position in HLA-DR proteins.

-	~~==Disease==~~	+	A polymorphic pocket at the P10 position contributes to peptide binding specificity in class II MHC proteins.,Zavala-Ruiz Z, Strug I, Anderson MW, Gorski J, Stern LJ Chem Biol. 2004 Oct;11(10):1395-402. PMID:15489166<ref>PMID:15489166</ref>
-	~~[[http://www.uniprot.org/uniprot/2B11_HUMAN 2B11_HUMAN]] Genetic variation~~ in ~~HLA-DRB1 is a cause of susceptibility to sarcoidosis type 1 (SS1) [MIM:[http://omim.org/entry/181000 181000]]~~. ~~Sarcoidosis is an idiopathic~~, ~~systemic~~, ~~inflammatory disease characterized by the formation of immune granulomas in involved organs. Granulomas predominantly invade the lungs and the lymphatic system~~, ~~but also skin~~, ~~liver~~, ~~spleen, eyes and other organs may be involved~~.<ref>PMID:~~14508706~~</ref>	+

-	~~==Function==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[http://www.uniprot.org/uniprot/ENTC3_STAAU ENTC3_STAAU]] Staphylococcal enterotoxins cause the intoxication staphylococcal food poisoning syndrome. The illness is characterized by high fever, hypotension, diarrhea, shock, and in some cases death. [[http://www.uniprot.org/uniprot/DRA_HUMAN DRA_HUMAN]] Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells. The peptide binding cleft accommodates peptides of 10-30 residues. The peptides presented by MHC class II molecules are generated mostly by degradation of proteins that access the endocytic route, where they are processed by lysosomal proteases and other hydrolases. Exogenous antigens that have been endocytosed by the APC are thus readily available for presentation via MHC II molecules, and for this reason this antigen presentation pathway is usually referred to as exogenous. As membrane proteins on their way to degradation in lysosomes as part of their normal turn-over are also contained in the endosomal/lysosomal compartments, exogenous antigens must compete with those derived from endogenous components. Autophagy is also a source of endogenous peptides, autophagosomes constitutively fuse with MHC class II loading compartments. In addition to APCs, other cells of the gastrointestinal tract, such as epithelial cells, express MHC class II molecules and CD74 and act as APCs, which is an unusual trait of the GI tract. To produce a MHC class II molecule that presents an antigen, three MHC class II molecules (heterodimers of an alpha and a beta chain) associate with a CD74 trimer in the ER to form a heterononamer. Soon after the entry of this complex into the endosomal/lysosomal system where antigen processing occurs, CD74 undergoes a sequential degradation by various proteases, including CTSS and CTSL, leaving a small fragment termed CLIP (class-II-associated invariant chain peptide). The removal of CLIP is facilitated by HLA-DM via direct binding to the alpha-beta-CLIP complex so that CLIP is released. HLA-DM stabilizes MHC class II molecules until primary high affinity antigenic peptides are bound. The MHC II molecule bound to a peptide is then transported to the cell membrane surface. In B-cells, the interaction between HLA-DM and MHC class II molecules is regulated by HLA-DO. Primary dendritic cells (DCs) also to express HLA-DO. Lysosomal miroenvironment has been implicated in the regulation of antigen loading into MHC II molecules, increased acidification produces increased proteolysis and efficient peptide loading. [[http://www.uniprot.org/uniprot/MIG1_YEAST MIG1_YEAST]] Involved in glucose repression of the SUC, GAL and MAL genes as well as of the CAT8 gene. Binds to two sites in the upstream region of SUC2. [[http://www.uniprot.org/uniprot/2B11_HUMAN 2B11_HUMAN]] Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells. The peptide binding cleft accommodates peptides of 10-30 residues. The peptides presented by MHC class II molecules are generated mostly by degradation of proteins that access the endocytic route; where they are processed by lysosomal proteases and other hydrolases. Exogenous antigens that have been endocytosed by the APC are thus readily available for presentation via MHC II molecules; and for this reason this antigen presentation pathway is usually referred to as exogenous. As membrane proteins on their way to degradation in lysosomes as part of their normal turn-over are also contained in the endosomal/~~lysosomal compartments~~; ~~exogenous antigens must compete with those derived from endogenous components. Autophagy is also~~ a ~~source of endogenous peptides; autophagosomes constitutively fuse with MHC class II loading compartments. In addition to APCs; other cells~~ of the ~~gastrointestinal tract; such as epithelial cells; express MHC class II molecules and CD74 and act as APCs; which is an unusual trait of the GI tract~~. ~~To produce a MHC class II molecule that presents an antigen; three MHC class II molecules (heterodimers of an alpha and a beta chain) associate with a CD74 trimer in the ER to form a heterononamer~~. ~~Soon after the entry~~ of this complex into the endosomal/lysosomal system where antigen processing occurs; CD74 undergoes a sequential degradation by various proteases; including CTSS and CTSL; leaving a small fragment termed CLIP (class-II-associated invariant chain peptide). The removal of CLIP is facilitated by HLA-DM via direct binding to the alpha-beta-CLIP complex so that CLIP is released. HLA-DM stabilizes MHC class II molecules until primary high affinity antigenic peptides are bound. The MHC II molecule bound to a peptide is then transported to the cell membrane surface. In B-cells; the interaction between HLA-DM and MHC class II molecules is regulated by HLA-DO. Primary dendritic cells (DCs) also to express HLA-DO. Lysosomal miroenvironment has been implicated in the regulation of antigen loading into MHC II molecules; increased acidification produces increased proteolysis and efficient peptide loading.	+	</div>
-		+
-	~~==About this Structure==~~	+
-	~~[[1t5x]] is a 4 chain structure with sequence from [http:~~//en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T5X OCA].	+

	==See Also==		==See Also==
	*[[Major histocompatibility complex\|Major histocompatibility complex]]		*[[Major histocompatibility complex\|Major histocompatibility complex]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	~~<ref group="xtra">PMID:015489166</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Staphylococcus aureus]]		[[Category: Staphylococcus aureus]]

OCA at 06:03, 25 March 2013

OCA — Mon, 25 Mar 2013 06:03:07 GMT

←Older revision		Revision as of 06:03, 25 March 2013
Line 1:		Line 1:
-	[[Image:1t5x.png\|left\|200px]]
-
	{{STRUCTURE_1t5x\| PDB=1t5x \| SCENE= }}		{{STRUCTURE_1t5x\| PDB=1t5x \| SCENE= }}
-
	===HLA-DR1 in complex with a synthetic peptide (AAYSDQATPLLLSPR) and the superantigen SEC3-3B2===		===HLA-DR1 in complex with a synthetic peptide (AAYSDQATPLLLSPR) and the superantigen SEC3-3B2===
		+	{{ABSTRACT_PUBMED_15489166}}

-	~~{{ABSTRACT_PUBMED_15489166}}~~	+	==Disease==
		+	[[http://www.uniprot.org/uniprot/2B11_HUMAN 2B11_HUMAN]] Genetic variation in HLA-DRB1 is a cause of susceptibility to sarcoidosis type 1 (SS1) [MIM:[http://omim.org/entry/181000 181000]]. Sarcoidosis is an idiopathic, systemic, inflammatory disease characterized by the formation of immune granulomas in involved organs. Granulomas predominantly invade the lungs and the lymphatic system, but also skin, liver, spleen, eyes and other organs may be involved.<ref>PMID:14508706</ref>
		+
		+	==Function==
		+	[[http://www.uniprot.org/uniprot/ENTC3_STAAU ENTC3_STAAU]] Staphylococcal enterotoxins cause the intoxication staphylococcal food poisoning syndrome. The illness is characterized by high fever, hypotension, diarrhea, shock, and in some cases death. [[http://www.uniprot.org/uniprot/DRA_HUMAN DRA_HUMAN]] Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells. The peptide binding cleft accommodates peptides of 10-30 residues. The peptides presented by MHC class II molecules are generated mostly by degradation of proteins that access the endocytic route, where they are processed by lysosomal proteases and other hydrolases. Exogenous antigens that have been endocytosed by the APC are thus readily available for presentation via MHC II molecules, and for this reason this antigen presentation pathway is usually referred to as exogenous. As membrane proteins on their way to degradation in lysosomes as part of their normal turn-over are also contained in the endosomal/lysosomal compartments, exogenous antigens must compete with those derived from endogenous components. Autophagy is also a source of endogenous peptides, autophagosomes constitutively fuse with MHC class II loading compartments. In addition to APCs, other cells of the gastrointestinal tract, such as epithelial cells, express MHC class II molecules and CD74 and act as APCs, which is an unusual trait of the GI tract. To produce a MHC class II molecule that presents an antigen, three MHC class II molecules (heterodimers of an alpha and a beta chain) associate with a CD74 trimer in the ER to form a heterononamer. Soon after the entry of this complex into the endosomal/lysosomal system where antigen processing occurs, CD74 undergoes a sequential degradation by various proteases, including CTSS and CTSL, leaving a small fragment termed CLIP (class-II-associated invariant chain peptide). The removal of CLIP is facilitated by HLA-DM via direct binding to the alpha-beta-CLIP complex so that CLIP is released. HLA-DM stabilizes MHC class II molecules until primary high affinity antigenic peptides are bound. The MHC II molecule bound to a peptide is then transported to the cell membrane surface. In B-cells, the interaction between HLA-DM and MHC class II molecules is regulated by HLA-DO. Primary dendritic cells (DCs) also to express HLA-DO. Lysosomal miroenvironment has been implicated in the regulation of antigen loading into MHC II molecules, increased acidification produces increased proteolysis and efficient peptide loading. [[http://www.uniprot.org/uniprot/MIG1_YEAST MIG1_YEAST]] Involved in glucose repression of the SUC, GAL and MAL genes as well as of the CAT8 gene. Binds to two sites in the upstream region of SUC2. [[http://www.uniprot.org/uniprot/2B11_HUMAN 2B11_HUMAN]] Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells. The peptide binding cleft accommodates peptides of 10-30 residues. The peptides presented by MHC class II molecules are generated mostly by degradation of proteins that access the endocytic route; where they are processed by lysosomal proteases and other hydrolases. Exogenous antigens that have been endocytosed by the APC are thus readily available for presentation via MHC II molecules; and for this reason this antigen presentation pathway is usually referred to as exogenous. As membrane proteins on their way to degradation in lysosomes as part of their normal turn-over are also contained in the endosomal/lysosomal compartments; exogenous antigens must compete with those derived from endogenous components. Autophagy is also a source of endogenous peptides; autophagosomes constitutively fuse with MHC class II loading compartments. In addition to APCs; other cells of the gastrointestinal tract; such as epithelial cells; express MHC class II molecules and CD74 and act as APCs; which is an unusual trait of the GI tract. To produce a MHC class II molecule that presents an antigen; three MHC class II molecules (heterodimers of an alpha and a beta chain) associate with a CD74 trimer in the ER to form a heterononamer. Soon after the entry of this complex into the endosomal/lysosomal system where antigen processing occurs; CD74 undergoes a sequential degradation by various proteases; including CTSS and CTSL; leaving a small fragment termed CLIP (class-II-associated invariant chain peptide). The removal of CLIP is facilitated by HLA-DM via direct binding to the alpha-beta-CLIP complex so that CLIP is released. HLA-DM stabilizes MHC class II molecules until primary high affinity antigenic peptides are bound. The MHC II molecule bound to a peptide is then transported to the cell membrane surface. In B-cells; the interaction between HLA-DM and MHC class II molecules is regulated by HLA-DO. Primary dendritic cells (DCs) also to express HLA-DO. Lysosomal miroenvironment has been implicated in the regulation of antigen loading into MHC II molecules; increased acidification produces increased proteolysis and efficient peptide loading.

	==About this Structure==		==About this Structure==
Line 14:		Line 16:

	==Reference==		==Reference==
-	<ref group="xtra">PMID:015489166</ref><references group="xtra"/>	+	<ref group="xtra">PMID:015489166</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Staphylococcus aureus]]		[[Category: Staphylococcus aureus]]

OCA at 09:14, 20 October 2012

OCA — Sat, 20 Oct 2012 09:14:27 GMT

←Older revision		Revision as of 09:14, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
-	[[1t5x]] is a 4 chain structure ~~of [[Major histocompatibility complex]]~~ with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T5X OCA].	+	[[1t5x]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T5X OCA].

	==See Also==		==See Also==

←Older revision		Revision as of 15:38, 27 October 2021
Line 3:		Line 3:
	<StructureSection load='1t5x' size='340' side='right'caption='[[1t5x]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='1t5x' size='340' side='right'caption='[[1t5x]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1t5x]] is a 4 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/"micrococcus_aureus"_(rosenbach_1884)_zopf_1885 "micrococcus aureus" (rosenbach 1884) zopf 1885] and [~~http~~://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T5X OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=1T5X FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1t5x]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/"micrococcus_aureus"_(rosenbach_1884)_zopf_1885 "micrococcus aureus" (rosenbach 1884) zopf 1885] and [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T5X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1T5X FirstGlance]. <br>
	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1aqd\|1aqd]], [[1dlh\|1dlh]], [[1klu\|1klu]], [[1pyw\|1pyw]], [[1t5w\|1t5w]]</div></td></tr>		</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1aqd\|1aqd]], [[1dlh\|1dlh]], [[1klu\|1klu]], [[1pyw\|1pyw]], [[1t5w\|1t5w]]</div></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HLA-DRA0101 ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), HLA-DRB10101 ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), SEC3 ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1280 "Micrococcus aureus" (Rosenbach 1884) Zopf 1885])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HLA-DRA0101 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), HLA-DRB10101 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), SEC3 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1280 "Micrococcus aureus" (Rosenbach 1884) Zopf 1885])</td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=1t5x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t5x OCA], [~~http~~://pdbe.org/1t5x PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=1t5x RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/1t5x PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=1t5x ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1t5x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t5x OCA], [https://pdbe.org/1t5x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1t5x RCSB], [https://www.ebi.ac.uk/pdbsum/1t5x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1t5x ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[~~http~~://www.uniprot.org/uniprot/2B11_HUMAN 2B11_HUMAN]] Genetic variation in HLA-DRB1 is a cause of susceptibility to sarcoidosis type 1 (SS1) [MIM:[~~http~~://omim.org/entry/181000 181000]]. Sarcoidosis is an idiopathic, systemic, inflammatory disease characterized by the formation of immune granulomas in involved organs. Granulomas predominantly invade the lungs and the lymphatic system, but also skin, liver, spleen, eyes and other organs may be involved.<ref>PMID:14508706</ref>	+	[[https://www.uniprot.org/uniprot/2B11_HUMAN 2B11_HUMAN]] Genetic variation in HLA-DRB1 is a cause of susceptibility to sarcoidosis type 1 (SS1) [MIM:[https://omim.org/entry/181000 181000]]. Sarcoidosis is an idiopathic, systemic, inflammatory disease characterized by the formation of immune granulomas in involved organs. Granulomas predominantly invade the lungs and the lymphatic system, but also skin, liver, spleen, eyes and other organs may be involved.<ref>PMID:14508706</ref>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/ENTC3_STAAU ENTC3_STAAU]] Staphylococcal enterotoxins cause the intoxication staphylococcal food poisoning syndrome. The illness is characterized by high fever, hypotension, diarrhea, shock, and in some cases death. [[~~http~~://www.uniprot.org/uniprot/DRA_HUMAN DRA_HUMAN]] Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells. The peptide binding cleft accommodates peptides of 10-30 residues. The peptides presented by MHC class II molecules are generated mostly by degradation of proteins that access the endocytic route, where they are processed by lysosomal proteases and other hydrolases. Exogenous antigens that have been endocytosed by the APC are thus readily available for presentation via MHC II molecules, and for this reason this antigen presentation pathway is usually referred to as exogenous. As membrane proteins on their way to degradation in lysosomes as part of their normal turn-over are also contained in the endosomal/lysosomal compartments, exogenous antigens must compete with those derived from endogenous components. Autophagy is also a source of endogenous peptides, autophagosomes constitutively fuse with MHC class II loading compartments. In addition to APCs, other cells of the gastrointestinal tract, such as epithelial cells, express MHC class II molecules and CD74 and act as APCs, which is an unusual trait of the GI tract. To produce a MHC class II molecule that presents an antigen, three MHC class II molecules (heterodimers of an alpha and a beta chain) associate with a CD74 trimer in the ER to form a heterononamer. Soon after the entry of this complex into the endosomal/lysosomal system where antigen processing occurs, CD74 undergoes a sequential degradation by various proteases, including CTSS and CTSL, leaving a small fragment termed CLIP (class-II-associated invariant chain peptide). The removal of CLIP is facilitated by HLA-DM via direct binding to the alpha-beta-CLIP complex so that CLIP is released. HLA-DM stabilizes MHC class II molecules until primary high affinity antigenic peptides are bound. The MHC II molecule bound to a peptide is then transported to the cell membrane surface. In B-cells, the interaction between HLA-DM and MHC class II molecules is regulated by HLA-DO. Primary dendritic cells (DCs) also to express HLA-DO. Lysosomal miroenvironment has been implicated in the regulation of antigen loading into MHC II molecules, increased acidification produces increased proteolysis and efficient peptide loading. [[~~http~~://www.uniprot.org/uniprot/MIG1_YEAST MIG1_YEAST]] Involved in glucose repression of the SUC, GAL and MAL genes as well as of the CAT8 gene. Binds to two sites in the upstream region of SUC2. [[~~http~~://www.uniprot.org/uniprot/2B11_HUMAN 2B11_HUMAN]] Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells. The peptide binding cleft accommodates peptides of 10-30 residues. The peptides presented by MHC class II molecules are generated mostly by degradation of proteins that access the endocytic route; where they are processed by lysosomal proteases and other hydrolases. Exogenous antigens that have been endocytosed by the APC are thus readily available for presentation via MHC II molecules; and for this reason this antigen presentation pathway is usually referred to as exogenous. As membrane proteins on their way to degradation in lysosomes as part of their normal turn-over are also contained in the endosomal/lysosomal compartments; exogenous antigens must compete with those derived from endogenous components. Autophagy is also a source of endogenous peptides; autophagosomes constitutively fuse with MHC class II loading compartments. In addition to APCs; other cells of the gastrointestinal tract; such as epithelial cells; express MHC class II molecules and CD74 and act as APCs; which is an unusual trait of the GI tract. To produce a MHC class II molecule that presents an antigen; three MHC class II molecules (heterodimers of an alpha and a beta chain) associate with a CD74 trimer in the ER to form a heterononamer. Soon after the entry of this complex into the endosomal/lysosomal system where antigen processing occurs; CD74 undergoes a sequential degradation by various proteases; including CTSS and CTSL; leaving a small fragment termed CLIP (class-II-associated invariant chain peptide). The removal of CLIP is facilitated by HLA-DM via direct binding to the alpha-beta-CLIP complex so that CLIP is released. HLA-DM stabilizes MHC class II molecules until primary high affinity antigenic peptides are bound. The MHC II molecule bound to a peptide is then transported to the cell membrane surface. In B-cells; the interaction between HLA-DM and MHC class II molecules is regulated by HLA-DO. Primary dendritic cells (DCs) also to express HLA-DO. Lysosomal miroenvironment has been implicated in the regulation of antigen loading into MHC II molecules; increased acidification produces increased proteolysis and efficient peptide loading.	+	[[https://www.uniprot.org/uniprot/ENTC3_STAAU ENTC3_STAAU]] Staphylococcal enterotoxins cause the intoxication staphylococcal food poisoning syndrome. The illness is characterized by high fever, hypotension, diarrhea, shock, and in some cases death. [[https://www.uniprot.org/uniprot/DRA_HUMAN DRA_HUMAN]] Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells. The peptide binding cleft accommodates peptides of 10-30 residues. The peptides presented by MHC class II molecules are generated mostly by degradation of proteins that access the endocytic route, where they are processed by lysosomal proteases and other hydrolases. Exogenous antigens that have been endocytosed by the APC are thus readily available for presentation via MHC II molecules, and for this reason this antigen presentation pathway is usually referred to as exogenous. As membrane proteins on their way to degradation in lysosomes as part of their normal turn-over are also contained in the endosomal/lysosomal compartments, exogenous antigens must compete with those derived from endogenous components. Autophagy is also a source of endogenous peptides, autophagosomes constitutively fuse with MHC class II loading compartments. In addition to APCs, other cells of the gastrointestinal tract, such as epithelial cells, express MHC class II molecules and CD74 and act as APCs, which is an unusual trait of the GI tract. To produce a MHC class II molecule that presents an antigen, three MHC class II molecules (heterodimers of an alpha and a beta chain) associate with a CD74 trimer in the ER to form a heterononamer. Soon after the entry of this complex into the endosomal/lysosomal system where antigen processing occurs, CD74 undergoes a sequential degradation by various proteases, including CTSS and CTSL, leaving a small fragment termed CLIP (class-II-associated invariant chain peptide). The removal of CLIP is facilitated by HLA-DM via direct binding to the alpha-beta-CLIP complex so that CLIP is released. HLA-DM stabilizes MHC class II molecules until primary high affinity antigenic peptides are bound. The MHC II molecule bound to a peptide is then transported to the cell membrane surface. In B-cells, the interaction between HLA-DM and MHC class II molecules is regulated by HLA-DO. Primary dendritic cells (DCs) also to express HLA-DO. Lysosomal miroenvironment has been implicated in the regulation of antigen loading into MHC II molecules, increased acidification produces increased proteolysis and efficient peptide loading. [[https://www.uniprot.org/uniprot/MIG1_YEAST MIG1_YEAST]] Involved in glucose repression of the SUC, GAL and MAL genes as well as of the CAT8 gene. Binds to two sites in the upstream region of SUC2. [[https://www.uniprot.org/uniprot/2B11_HUMAN 2B11_HUMAN]] Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells. The peptide binding cleft accommodates peptides of 10-30 residues. The peptides presented by MHC class II molecules are generated mostly by degradation of proteins that access the endocytic route; where they are processed by lysosomal proteases and other hydrolases. Exogenous antigens that have been endocytosed by the APC are thus readily available for presentation via MHC II molecules; and for this reason this antigen presentation pathway is usually referred to as exogenous. As membrane proteins on their way to degradation in lysosomes as part of their normal turn-over are also contained in the endosomal/lysosomal compartments; exogenous antigens must compete with those derived from endogenous components. Autophagy is also a source of endogenous peptides; autophagosomes constitutively fuse with MHC class II loading compartments. In addition to APCs; other cells of the gastrointestinal tract; such as epithelial cells; express MHC class II molecules and CD74 and act as APCs; which is an unusual trait of the GI tract. To produce a MHC class II molecule that presents an antigen; three MHC class II molecules (heterodimers of an alpha and a beta chain) associate with a CD74 trimer in the ER to form a heterononamer. Soon after the entry of this complex into the endosomal/lysosomal system where antigen processing occurs; CD74 undergoes a sequential degradation by various proteases; including CTSS and CTSL; leaving a small fragment termed CLIP (class-II-associated invariant chain peptide). The removal of CLIP is facilitated by HLA-DM via direct binding to the alpha-beta-CLIP complex so that CLIP is released. HLA-DM stabilizes MHC class II molecules until primary high affinity antigenic peptides are bound. The MHC II molecule bound to a peptide is then transported to the cell membrane surface. In B-cells; the interaction between HLA-DM and MHC class II molecules is regulated by HLA-DO. Primary dendritic cells (DCs) also to express HLA-DO. Lysosomal miroenvironment has been implicated in the regulation of antigen loading into MHC II molecules; increased acidification produces increased proteolysis and efficient peptide loading.
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]