4md4 - Revision history

OCA at 09:19, 15 November 2023

2023-11-15T09:19:54Z

←Older revision		Revision as of 09:19, 15 November 2023
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4md4]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MD4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MD4 FirstGlance]. <br>		<table><tr><td colspan='2'>[[4md4]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MD4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MD4 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CIR:CITRULLINE'>CIR</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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]] 1.95Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CIR:CITRULLINE'>CIR</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=4md4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4md4 OCA], [https://pdbe.org/4md4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4md4 RCSB], [https://www.ebi.ac.uk/pdbsum/4md4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4md4 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=4md4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4md4 OCA], [https://pdbe.org/4md4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4md4 RCSB], [https://www.ebi.ac.uk/pdbsum/4md4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4md4 ProSAT]</span></td></tr>
	</table>		</table>

OCA at 11:10, 21 December 2022

2022-12-21T11:10:31Z

←Older revision		Revision as of 11:10, 21 December 2022
Line 1:		Line 1:

	==Immune Receptor==		==Immune Receptor==
-	<StructureSection load='4md4' size='340' side='right' caption='[[4md4]], [[Resolution\|resolution]] 1.95Å' scene=''>	+	<StructureSection load='4md4' size='340' side='right'caption='[[4md4]], [[Resolution\|resolution]] 1.95Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4md4]] is a 3 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MD4 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4MD4 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4md4]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MD4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MD4 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>~~</td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CIR:CITRULLINE'>CIR</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
-	~~<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CIR:CITRULLINE'>CIR</scene></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=4md4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4md4 OCA], [https://pdbe.org/4md4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4md4 RCSB], [https://www.ebi.ac.uk/pdbsum/4md4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4md4 ProSAT]</span></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4mcy\|4mcy]], [[4mcz\|4mcz]], [[4md0\|4md0]], [[4md5\|4md5]], [[4mdi\|4mdi]], [[4mdj\|4mdj]]</td></tr>	+
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HLA-DRA, HLA-DRA1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), HLA-DRB1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4md4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4md4 OCA], [~~http~~://pdbe.org/4md4 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4md4 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4md4 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4md4 ProSAT]</span></td></tr>	+
	</table>		</table>
-	== Disease ==
-	[[http://www.uniprot.org/uniprot/PGCA_HUMAN PGCA_HUMAN]] Spondyloepimetaphyseal dysplasia, aggrecan type;Spondyloepiphyseal dysplasia, Kimberley type;Familial osteochondritis dissecans. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry.
	== Function ==		== Function ==
-	[~~[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/PGCA_HUMAN PGCA_HUMAN]] This proteoglycan is a major component of extracellular matrix of cartilagenous tissues. A major function of this protein is to resist compression in cartilage. It binds avidly to hyaluronic acid via an N-terminal globular region. [[http://www.uniprot.org/uniprot/2B14_HUMAN 2B14_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.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 27:		Line 22:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Rossjohn, J~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Scally, S W~~]]	+	[[Category: Rossjohn J]]
-	[[Category: ~~Antigen presentation]]~~	+	[[Category: Scally SW]]
-	~~[[Category: Citrullination]]~~	+
-	~~[[Category: Hla-dr]]~~	+
-	~~[[Category: Immune system]]~~	+
-	~~[[Category: Membrane]]~~	+
-	~~[[Category: T-cell receptor~~]]	+

OCA at 07:28, 23 December 2016

2016-12-23T07:28:21Z

←Older revision		Revision as of 07:28, 23 December 2016
Line 1:		Line 1:
		+
	==Immune Receptor==		==Immune Receptor==
	<StructureSection load='4md4' size='340' side='right' caption='[[4md4]], [[Resolution\|resolution]] 1.95Å' scene=''>		<StructureSection load='4md4' size='340' side='right' caption='[[4md4]], [[Resolution\|resolution]] 1.95Å' scene=''>
Line 7:		Line 8:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4mcy\|4mcy]], [[4mcz\|4mcz]], [[4md0\|4md0]], [[4md5\|4md5]], [[4mdi\|4mdi]], [[4mdj\|4mdj]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4mcy\|4mcy]], [[4mcz\|4mcz]], [[4md0\|4md0]], [[4md5\|4md5]], [[4mdi\|4mdi]], [[4mdj\|4mdj]]</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HLA-DRA, HLA-DRA1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), HLA-DRB1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HLA-DRA, HLA-DRA1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), HLA-DRB1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4md4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4md4 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4md4 RCSB], [http://www.ebi.ac.uk/pdbsum/4md4 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=4md4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4md4 OCA], [http://pdbe.org/4md4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4md4 RCSB], [http://www.ebi.ac.uk/pdbsum/4md4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4md4 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 21:		Line 22:
	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 4md4" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 08:53, 15 February 2015

2015-02-15T08:53:45Z

←Older revision		Revision as of 08:53, 15 February 2015
Line 1:		Line 1:
-	~~{{STRUCTURE_4md4~~\| ~~PDB~~=4md4 \| ~~SCENE~~= }}	+	==Immune Receptor==
-	===~~Immune Receptor~~===	+	<StructureSection load='4md4' size='340' side='right' caption='[[4md4]], [[Resolution\|resolution]] 1.95Å' scene=''>
-	~~{{ABSTRACT_PUBMED_24190431}}~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[4md4]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MD4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4MD4 FirstGlance]. <br>
-	==Disease==	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
		+	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CIR:CITRULLINE'>CIR</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4mcy\|4mcy]], [[4mcz\|4mcz]], [[4md0\|4md0]], [[4md5\|4md5]], [[4mdi\|4mdi]], [[4mdj\|4mdj]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HLA-DRA, HLA-DRA1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), HLA-DRB1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4md4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4md4 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4md4 RCSB], [http://www.ebi.ac.uk/pdbsum/4md4 PDBsum]</span></td></tr>
		+	</table>
		+	== Disease ==
	[[http://www.uniprot.org/uniprot/PGCA_HUMAN PGCA_HUMAN]] Spondyloepimetaphyseal dysplasia, aggrecan type;Spondyloepiphyseal dysplasia, Kimberley type;Familial osteochondritis dissecans. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry.		[[http://www.uniprot.org/uniprot/PGCA_HUMAN PGCA_HUMAN]] Spondyloepimetaphyseal dysplasia, aggrecan type;Spondyloepiphyseal dysplasia, Kimberley type;Familial osteochondritis dissecans. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry.
-		+	== Function ==
-	==Function==	+
	[[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/PGCA_HUMAN PGCA_HUMAN]] This proteoglycan is a major component of extracellular matrix of cartilagenous tissues. A major function of this protein is to resist compression in cartilage. It binds avidly to hyaluronic acid via an N-terminal globular region. [[http://www.uniprot.org/uniprot/2B14_HUMAN 2B14_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/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/PGCA_HUMAN PGCA_HUMAN]] This proteoglycan is a major component of extracellular matrix of cartilagenous tissues. A major function of this protein is to resist compression in cartilage. It binds avidly to hyaluronic acid via an N-terminal globular region. [[http://www.uniprot.org/uniprot/2B14_HUMAN 2B14_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 style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Rheumatoid arthritis (RA) is strongly associated with the human leukocyte antigen (HLA)-DRB1 locus that possesses the shared susceptibility epitope (SE) and the citrullination of self-antigens. We show how citrullinated aggrecan and vimentin epitopes bind to HLA-DRB104:01/04. Citrulline was accommodated within the electropositive P4 pocket of HLA-DRB104:01/04, whereas the electronegative P4 pocket of the RA-resistant HLA-DRB104:02 allomorph interacted with arginine or citrulline-containing epitopes. Peptide elution studies revealed P4 arginine-containing peptides from HLA-DRB104:02, but not from HLA-DRB104:01/04. Citrullination altered protease susceptibility of vimentin, thereby generating self-epitopes that are presented to T cells in HLA-DRB104:01(+) individuals. Using HLA-II tetramers, we observed citrullinated vimentin- and aggrecan-specific CD4(+) T cells in the peripheral blood of HLA-DRB1*04:01(+) RA-affected and healthy individuals. In RA patients, autoreactive T cell numbers correlated with disease activity and were deficient in regulatory T cells relative to healthy individuals. These findings reshape our understanding of the association between citrullination, the HLA-DRB1 locus, and T cell autoreactivity in RA.

-	~~==About this Structure==~~	+	A molecular basis for the association of the HLA-DRB1 locus, citrullination, and rheumatoid arthritis.,Scally SW, Petersen J, Law SC, Dudek NL, Nel HJ, Loh KL, Wijeyewickrema LC, Eckle SB, van Heemst J, Pike RN, McCluskey J, Toes RE, La Gruta NL, Purcell AW, Reid HH, Thomas R, Rossjohn J J Exp Med. 2013 Nov 18;210(12):2569-82. doi: 10.1084/jem.20131241. Epub 2013 Nov , 4. PMID:24190431<ref>PMID:24190431</ref>
-	~~[[4md4]] is a 3 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Human Human]~~. ~~Full crystallographic information is available from [http~~:/~~/oca~~.~~weizmann~~.ac.il/~~oca-bin/ocashort?id=4MD4 OCA].~~	+

-	==~~Reference~~==	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~<ref group="xtra">PMID:024190431</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	</div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Human]]		[[Category: Human]]
-	[[Category: Rossjohn, J.]]	+	[[Category: Rossjohn, J]]
-	[[Category: Scally, S W.]]	+	[[Category: Scally, S W]]
	[[Category: Antigen presentation]]		[[Category: Antigen presentation]]
	[[Category: Citrullination]]		[[Category: Citrullination]]

OCA at 12:30, 11 December 2013

2013-12-11T12:30:14Z

←Older revision		Revision as of 12:30, 11 December 2013
Line 10:		Line 10:

	==About this Structure==		==About this Structure==
-	[[4md4]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MD4 OCA].	+	[[4md4]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MD4 OCA].

	==Reference==		==Reference==
	<ref group="xtra">PMID:024190431</ref><references group="xtra"/><references/>		<ref group="xtra">PMID:024190431</ref><references group="xtra"/><references/>
		+	[[Category: Human]]
	[[Category: Rossjohn, J.]]		[[Category: Rossjohn, J.]]
	[[Category: Scally, S W.]]		[[Category: Scally, S W.]]

OCA at 07:23, 4 December 2013

2013-12-04T07:23:36Z

←Older revision		Revision as of 07:23, 4 December 2013
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	{{STRUCTURE_4md4\| PDB=4md4 \| SCENE= }}
		+	===Immune Receptor===
		+	{{ABSTRACT_PUBMED_24190431}}

-	The entry ~~4md4~~ is ~~ON HOLD~~	+	==Disease==
		+	[[http://www.uniprot.org/uniprot/PGCA_HUMAN PGCA_HUMAN]] Spondyloepimetaphyseal dysplasia, aggrecan type;Spondyloepiphyseal dysplasia, Kimberley type;Familial osteochondritis dissecans. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry.

-	~~Authors~~: ~~Scally~~, S.W., ~~Rossjohn~~, J.	+	==Function==
		+	[[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/PGCA_HUMAN PGCA_HUMAN]] This proteoglycan is a major component of extracellular matrix of cartilagenous tissues. A major function of this protein is to resist compression in cartilage. It binds avidly to hyaluronic acid via an N-terminal globular region. [[http://www.uniprot.org/uniprot/2B14_HUMAN 2B14_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.

-	~~Description~~: Immune ~~Receptor~~	+	==About this Structure==
		+	[[4md4]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MD4 OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:024190431</ref><references group="xtra"/><references/>
		+	[[Category: Rossjohn, J.]]
		+	[[Category: Scally, S W.]]
		+	[[Category: Antigen presentation]]
		+	[[Category: Citrullination]]
		+	[[Category: Hla-dr]]
		+	[[Category: Immune system]]
		+	[[Category: Membrane]]
		+	[[Category: T-cell receptor]]

OCA at 03:37, 20 September 2013

2013-09-20T03:37:12Z

←Older revision		Revision as of 03:37, 20 September 2013
Line 3:		Line 3:
	The entry 4md4 is ON HOLD		The entry 4md4 is ON HOLD

-	Authors: Scally,S.W., Rossjohn,J.	+	Authors: Scally, S.W., Rossjohn, J.

	Description: Immune Receptor		Description: Immune Receptor

OCA: Protected "4md4" [edit=sysop:move=sysop]

2013-08-28T06:59:26Z

Protected "4md4" [edit=sysop:move=sysop]

←Older revision

Revision as of 06:59, 28 August 2013

OCA: New page: '''Unreleased structure''' The entry 4md4 is ON HOLD Authors: Scally,S.W., Rossjohn,J. Description: Immune Receptor

2013-08-28T06:59:25Z

New page: '''Unreleased structure''' The entry 4md4 is ON HOLD Authors: Scally,S.W., Rossjohn,J. Description: Immune Receptor

New page

'''Unreleased structure'''

The entry 4md4 is ON HOLD

Authors: Scally,S.W., Rossjohn,J.

Description: Immune Receptor