4p4k - Revision history

OCA at 07:11, 27 September 2023

OCA — Wed, 27 Sep 2023 07:11:06 GMT

←Older revision		Revision as of 07:11, 27 September 2023
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4p4k]] is a 8 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=4P4K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4P4K FirstGlance]. <br>		<table><tr><td colspan='2'>[[4p4k]] is a 8 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=4P4K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4P4K FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0BE:BERYLLIUM'>0BE</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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]] 2.8Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0BE:BERYLLIUM'>0BE</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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=4p4k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p4k OCA], [https://pdbe.org/4p4k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4p4k RCSB], [https://www.ebi.ac.uk/pdbsum/4p4k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4p4k 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=4p4k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p4k OCA], [https://pdbe.org/4p4k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4p4k RCSB], [https://www.ebi.ac.uk/pdbsum/4p4k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4p4k ProSAT]</span></td></tr>
	</table>		</table>

OCA at 12:41, 1 February 2023

OCA — Wed, 01 Feb 2023 12:41:38 GMT

←Older revision		Revision as of 12:41, 1 February 2023
Line 3:		Line 3:
	<StructureSection load='4p4k' size='340' side='right'caption='[[4p4k]], [[Resolution\|resolution]] 2.80Å' scene=''>		<StructureSection load='4p4k' size='340' side='right'caption='[[4p4k]], [[Resolution\|resolution]] 2.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4p4k]] is a 8 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=4P4K OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4P4K FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4p4k]] is a 8 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=4P4K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4P4K FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0BE:BERYLLIUM'>0BE</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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=0BE:BERYLLIUM'>0BE</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4p4r\|4p4r]], [[4p57\|4p57]], [[4p5m\|4p5m]], [[4p5k\|4p5k]]</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=4p4k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p4k OCA], [https://pdbe.org/4p4k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4p4k RCSB], [https://www.ebi.ac.uk/pdbsum/4p4k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4p4k ProSAT]</span></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HLA-DPA1, HLA-DP1A, HLASB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), HLA-DPB1, HLA-DP1B ([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=4p4k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p4k OCA], [~~http~~://pdbe.org/4p4k PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4p4k RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4p4k PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4p4k ProSAT]</span></td></tr>	+
	</table>		</table>
		+	== Disease ==
		+	[https://www.uniprot.org/uniprot/DPB1_HUMAN DPB1_HUMAN] Chronic beryllium disease;Granulomatosis with polyangiitis.
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/~~DPA1_HUMAN DPA1_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/DPB1_HUMAN DPB1_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 microenvironment 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 24:		Line 24:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Clayton~~, G M~~]]	+	[[Category: Clayton GM]]
-	[[Category: Crawford, F]]	+	[[Category: Crawford F]]
-	[[Category: Kappler~~, J W]]~~	+	[[Category: Kappler JW]]
-	~~[[Category: Be bound complex]]~~	+
-	~~[[Category: Chronic beryllium disease]]~~	+
-	~~[[Category: Immune system]]~~	+
-	~~[[Category: Tcr-mhc peptide-be2+~~]]	+

OCA at 07:25, 17 April 2019

OCA — Wed, 17 Apr 2019 07:25:13 GMT

←Older revision		Revision as of 07:25, 17 April 2019
Line 1:		Line 1:

	==Structural Basis of Chronic Beryllium Disease: Bridging the Gap Between allergic hypersensitivity and auto immunity==		==Structural Basis of Chronic Beryllium Disease: Bridging the Gap Between allergic hypersensitivity and auto immunity==
-	<StructureSection load='4p4k' size='340' side='right' caption='[[4p4k]], [[Resolution\|resolution]] 2.80Å' scene=''>	+	<StructureSection load='4p4k' size='340' side='right'caption='[[4p4k]], [[Resolution\|resolution]] 2.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4p4k]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4P4K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4P4K FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4p4k]] is a 8 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=4P4K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4P4K FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0BE:BERYLLIUM'>0BE</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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"><scene name='pdbligand=0BE:BERYLLIUM'>0BE</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4p4r\|4p4r]], [[4p57\|4p57]], [[4p5m\|4p5m]], [[4p5k\|4p5k]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4p4r\|4p4r]], [[4p57\|4p57]], [[4p5m\|4p5m]], [[4p5k\|4p5k]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HLA-DPA1, HLA-DP1A, HLASB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), HLA-DPB1, HLA-DP1B ([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=4p4k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p4k OCA], [http://pdbe.org/4p4k PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4p4k RCSB], [http://www.ebi.ac.uk/pdbsum/4p4k PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4p4k ProSAT]</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=4p4k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p4k OCA], [http://pdbe.org/4p4k PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4p4k RCSB], [http://www.ebi.ac.uk/pdbsum/4p4k PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4p4k ProSAT]</span></td></tr>
	</table>		</table>
Line 23:		Line 24:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Clayton, G M]]		[[Category: Clayton, G M]]
	[[Category: Crawford, F]]		[[Category: Crawford, F]]

OCA at 08:12, 11 August 2016

OCA — Thu, 11 Aug 2016 08:12:57 GMT

←Older revision		Revision as of 08:12, 11 August 2016
Line 1:		Line 1:
		+
	==Structural Basis of Chronic Beryllium Disease: Bridging the Gap Between allergic hypersensitivity and auto immunity==		==Structural Basis of Chronic Beryllium Disease: Bridging the Gap Between allergic hypersensitivity and auto immunity==
	<StructureSection load='4p4k' size='340' side='right' caption='[[4p4k]], [[Resolution\|resolution]] 2.80Å' scene=''>		<StructureSection load='4p4k' size='340' side='right' caption='[[4p4k]], [[Resolution\|resolution]] 2.80Å' scene=''>
Line 5:		Line 6:
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0BE:BERYLLIUM'>0BE</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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"><scene name='pdbligand=0BE:BERYLLIUM'>0BE</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4p4r\|4p4r]], [[4p57\|4p57]], [[4p5m\|4p5m]], [[4p5k\|4p5k]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4p4r\|4p4r]], [[4p57\|4p57]], [[4p5m\|4p5m]], [[4p5k\|4p5k]]</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=4p4k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p4k OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4p4k RCSB], [http://www.ebi.ac.uk/pdbsum/4p4k 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=4p4k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p4k OCA], [http://pdbe.org/4p4k PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4p4k RCSB], [http://www.ebi.ac.uk/pdbsum/4p4k PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4p4k ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 17:		Line 18:
	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 4p4k" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 07:24, 25 December 2014

OCA — Thu, 25 Dec 2014 07:24:12 GMT

←Older revision		Revision as of 07:24, 25 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4p4k]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4P4K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4P4K FirstGlance]. <br>		<table><tr><td colspan='2'>[[4p4k]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4P4K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4P4K FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0BE:BERYLLIUM'>0BE</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0BE:BERYLLIUM'>0BE</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4p4r\|4p4r]], [[4p57\|4p57]], [[4p5m\|4p5m]], [[4p5k\|4p5k]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4p4r\|4p4r]], [[4p57\|4p57]], [[4p5m\|4p5m]], [[4p5k\|4p5k]]</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=4p4k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p4k OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4p4k RCSB], [http://www.ebi.ac.uk/pdbsum/4p4k 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=4p4k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p4k OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4p4k RCSB], [http://www.ebi.ac.uk/pdbsum/4p4k PDBsum]</span></td></tr>
-	<table>	+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/DPA1_HUMAN DPA1_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 19:		Line 21:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Clayton, G M.]]	+	[[Category: Clayton, G M]]
-	[[Category: Crawford, F.]]	+	[[Category: Crawford, F]]
-	[[Category: Kappler, J W.]]	+	[[Category: Kappler, J W]]
	[[Category: Be bound complex]]		[[Category: Be bound complex]]
	[[Category: Chronic beryllium disease]]		[[Category: Chronic beryllium disease]]
	[[Category: Immune system]]		[[Category: Immune system]]
	[[Category: Tcr-mhc peptide-be2+]]		[[Category: Tcr-mhc peptide-be2+]]

OCA at 10:19, 16 July 2014

OCA — Wed, 16 Jul 2014 10:19:39 GMT

←Older revision		Revision as of 10:19, 16 July 2014
Line 1:		Line 1:
-	'''~~Unreleased~~ structure'''	+	==Structural Basis of Chronic Beryllium Disease: Bridging the Gap Between allergic hypersensitivity and auto immunity==
		+	<StructureSection load='4p4k' size='340' side='right' caption='[[4p4k]], [[Resolution\|resolution]] 2.80Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4p4k]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4P4K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4P4K FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0BE:BERYLLIUM'>0BE</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4p4r\|4p4r]], [[4p57\|4p57]], [[4p5m\|4p5m]], [[4p5k\|4p5k]]</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=4p4k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p4k OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4p4k RCSB], [http://www.ebi.ac.uk/pdbsum/4p4k PDBsum]</span></td></tr>
		+	<table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	T-cell-mediated hypersensitivity to metal cations is common in humans. How the T cell antigen receptor (TCR) recognizes these cations bound to a major histocompatibility complex (MHC) protein and self-peptide is unknown. Individuals carrying the MHCII allele, HLA-DP2, are at risk for chronic beryllium disease (CBD), a debilitating inflammatory lung condition caused by the reaction of CD4 T cells to inhaled beryllium. Here, we show that the T cell ligand is created when a Be(2+) cation becomes buried in an HLA-DP2/peptide complex, where it is coordinated by both MHC and peptide acidic amino acids. Surprisingly, the TCR does not interact with the Be(2+) itself, but rather with surface changes induced by the firmly bound Be(2+) and an accompanying Na(+) cation. Thus, CBD, by creating a new antigen by indirectly modifying the structure of preexisting self MHC-peptide complex, lies on the border between allergic hypersensitivity and autoimmunity.

-	~~The entry 4p4k is ON HOLD until Paper Publication~~	+	Structural basis of chronic beryllium disease: linking allergic hypersensitivity and autoimmunity.,Clayton GM, Wang Y, Crawford F, Novikov A, Wimberly BT, Kieft JS, Falta MT, Bowerman NA, Marrack P, Fontenot AP, Dai S, Kappler JW Cell. 2014 Jul 3;158(1):132-42. doi: 10.1016/j.cell.2014.04.048. PMID:24995984<ref>PMID:24995984</ref>

-	~~Authors~~: Clayton, G.M., Crawford, F., Kappler, J.W.	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~Description~~: ~~Structural Basis of~~ Chronic ~~Beryllium Disease~~: ~~Bridging the Gap Between allergic hypersensitivity and auto immunity~~	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Clayton, G M.]]
		+	[[Category: Crawford, F.]]
		+	[[Category: Kappler, J W.]]
		+	[[Category: Be bound complex]]
		+	[[Category: Chronic beryllium disease]]
		+	[[Category: Immune system]]
		+	[[Category: Tcr-mhc peptide-be2+]]

OCA at 09:02, 16 April 2014

OCA — Wed, 16 Apr 2014 09:02:35 GMT

←Older revision		Revision as of 09:02, 16 April 2014
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4p4k is ON HOLD	+	The entry 4p4k is ON HOLD until Paper Publication

	Authors: Clayton, G.M., Crawford, F., Kappler, J.W.		Authors: Clayton, G.M., Crawford, F., Kappler, J.W.

-	Description: Structural Basis of Chronic Beryllium Disease: Bridging the Gap Between ~~Allergy~~ and ~~Autoimmunity~~	+	Description: Structural Basis of Chronic Beryllium Disease: Bridging the Gap Between allergic hypersensitivity and auto immunity

OCA at 05:52, 9 April 2014

OCA — Wed, 09 Apr 2014 05:52:08 GMT

←Older revision		Revision as of 05:52, 9 April 2014
Line 3:		Line 3:
	The entry 4p4k is ON HOLD		The entry 4p4k is ON HOLD

-	Authors: Clayton G.M. Crawford F. Kappler J.W.	+	Authors: Clayton, G.M., Crawford, F., Kappler, J.W.

-	Description: Structural Basis of Chronic Beryllium Disease:	+	Description: Structural Basis of Chronic Beryllium Disease: Bridging the Gap Between Allergy and Autoimmunity

OCA: Protected "4p4k" [edit=sysop:move=sysop]

OCA — Wed, 19 Mar 2014 07:34:48 GMT

Protected "4p4k" [edit=sysop:move=sysop]

←Older revision

Revision as of 07:34, 19 March 2014

OCA: New page: '''Unreleased structure''' The entry 4p4k is ON HOLD Authors: Clayton G.M. Crawford F. Kappler J.W. Description: Structural Basis of Chronic Beryllium Disease:

OCA — Wed, 19 Mar 2014 07:34:46 GMT

New page: '''Unreleased structure''' The entry 4p4k is ON HOLD Authors: Clayton G.M. Crawford F. Kappler J.W. Description: Structural Basis of Chronic Beryllium Disease:

New page

'''Unreleased structure'''

The entry 4p4k is ON HOLD

Authors: Clayton G.M. Crawford F. Kappler J.W.

Description: Structural Basis of Chronic Beryllium Disease: