4qok - Revision history

OCA at 17:34, 20 September 2023

OCA — Wed, 20 Sep 2023 17:34:24 GMT

←Older revision		Revision as of 17:34, 20 September 2023
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4qok]] is a 5 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=4QOK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QOK FirstGlance]. <br>		<table><tr><td colspan='2'>[[4qok]] is a 5 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=4QOK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QOK FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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]] 3Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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=4qok FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qok OCA], [https://pdbe.org/4qok PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qok RCSB], [https://www.ebi.ac.uk/pdbsum/4qok PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qok 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=4qok FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qok OCA], [https://pdbe.org/4qok PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qok RCSB], [https://www.ebi.ac.uk/pdbsum/4qok PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qok ProSAT]</span></td></tr>
	</table>		</table>

OCA at 13:44, 22 February 2023

OCA — Wed, 22 Feb 2023 13:44:07 GMT

←Older revision		Revision as of 13:44, 22 February 2023
Line 1:		Line 1:

	==Structural basis for ineffective T-cell responses to MHC anchor residue improved heteroclitic peptides==		==Structural basis for ineffective T-cell responses to MHC anchor residue improved heteroclitic peptides==
-	<StructureSection load='4qok' size='340' side='right' caption='[[4qok]], [[Resolution\|resolution]] 3.00Å' scene=''>	+	<StructureSection load='4qok' size='340' side='right'caption='[[4qok]], [[Resolution\|resolution]] 3.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4qok]] is a 5 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=4QOK OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4QOK FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4qok]] is a 5 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=4QOK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QOK 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>~~</td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3hg1\|3hg1]], [[4jfd\|4jfd]]</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=4qok FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qok OCA], [https://pdbe.org/4qok PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qok RCSB], [https://www.ebi.ac.uk/pdbsum/4qok PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qok ProSAT]</span></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HLA-A, HLAA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), B2M, CDABP0092, HDCMA22P ([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=4qok FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qok OCA], [~~http~~://pdbe.org/4qok PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4qok RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4qok PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4qok ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/~~B2MG_HUMAN B2MG_HUMAN~~]~~] Defects~~ in ~~B2M~~ are ~~the cause of hypercatabolic hypoproteinemia~~ (~~HYCATHYP~~) ~~[MIM~~:~~[http~~:~~//omim.org/entry/241600 241600]]. Affected individuals show marked reduction in serum concentrations of immunoglobulin and albumin~~, ~~probably due to rapid degradation.<ref>PMID~~:~~16549777</ref> Note=Beta-2~~-~~microglobulin~~ may ~~adopt~~ the ~~fibrillar configuration~~ of ~~amyloid~~ in ~~certain pathologic states~~. ~~The capacity to assemble into amyloid fibrils is concentration dependent. Persistently high beta~~(2)~~-microglobulin serum levels lead~~ to ~~amyloidosis in patients on long~~-~~term hemodialysis~~.<ref>PMID:~~3532124~~</ref> <ref>PMID:~~1336137~~</ref> <ref>PMID:~~7554280~~</ref> <ref>PMID:~~4586824~~</ref> ~~<ref>PMID~~:~~8084451</ref> <ref>PMID~~:~~12119416</ref> <ref>PMID~~:~~12796775</ref>~~ <ref>PMID:~~16901902~~</ref> <ref>PMID:~~16491088~~</ref> ~~<ref>PMID~~:~~17646174</ref>~~ <ref>PMID:~~18835253~~</ref> ~~<ref>PMID~~:~~18395224</ref>~~ <ref>PMID:~~19284997~~</ref>	+	[https://www.uniprot.org/uniprot/HLAA_HUMAN HLAA_HUMAN] Selection of immunotherapy in solid cancer;Birdshot chorioretinopathy;Prediction of phenytoin or carbamazepine toxicity. Alleles A02:01 and A24:02 are associated with increased susceptibility to diabetes mellitus, insulin-dependent (IDDM) (PubMed:22245737, PubMed:18802479, PubMed:16731854, PubMed:22522618). In a glucose-dependent way, allele A02:01 may aberrantly present the signal peptide of preproinsulin (ALWGPDPAAA) on the surface of pancreatic beta cells to autoreactive CD8-positive T cells, potentially driving T-cell mediated cytotoxicity in pancreatic islets (PubMed:22245737, PubMed:18802479). Allele A24:02 may present the signal peptide of preproinsulin (LWMRLLPLL) and contribute to acute pancreatic beta-cell destruction and early onset of IDDM (PubMed:16731854, PubMed:22522618).<ref>PMID:16731854</ref> <ref>PMID:18802479</ref> <ref>PMID:22245737</ref> <ref>PMID:22522618</ref> Allele A03:01 is associated with increased susceptibility to multiple sclerosis (MS), an autoimmune disease of the central nervous system (PubMed:10746785). May contribute to the initiation phase of the disease by presenting myelin PLP1 self-peptide (KLIETYFSK) to autoreactive CD8-positive T cells capable of initiating the first autoimmune attacks (PubMed:18953350).<ref>PMID:10746785</ref> <ref>PMID:18953350</ref> Allele A26:01 is associated with increased susceptibility to Behcet disease (BD) in the Northeast Asian population. Especially in the HLA-B51-negative BD populations, HLA-A26 is significantly associated with the onset of BD.<ref>PMID:30872678</ref> Allele A*29:02 is associated with increased susceptibility to birdshot chorioretinopathy (BSCR). May aberrantly present retinal autoantigens and induce autoimmune uveitis.<ref>PMID:1728143</ref>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/~~1A02_HUMAN 1A02_HUMAN~~]~~] Involved in~~ the ~~presentation~~ of ~~foreign antigens~~ to ~~the immune system~~. ~~[[http~~:/~~/www~~.~~uniprot~~.~~org~~/~~uniprot~~/~~MAR1_HUMAN MAR1_HUMAN]] Involved~~ in ~~melanosome biogenesis by ensuring~~ the ~~stability of GPR143~~. ~~Plays~~ a ~~vital role in~~ the ~~expression~~, ~~stability~~, ~~trafficking~~, and ~~processing of melanocyte protein PMEL~~, ~~which is critical to~~ the ~~formation of stage II melanosomes~~.<ref>PMID:~~15695812~~</ref> <ref>PMID:~~19717472~~</ref> ~~[[http~~://~~www.uniprot.org~~/~~uniprot~~/~~B2MG_HUMAN B2MG_HUMAN]] Component~~ of the ~~class I major histocompatibility complex~~ (~~MHC~~). ~~Involved~~ in the ~~presentation~~ of peptide antigens to the immune ~~system~~.	+	[https://www.uniprot.org/uniprot/HLAA_HUMAN HLAA_HUMAN] Antigen-presenting major histocompatibility complex class I (MHCI) molecule. In complex with B2M/beta 2 microglobulin displays primarily viral and tumor-derived peptides on antigen-presenting cells for recognition by alpha-beta T cell receptor (TCR) on HLA-A-restricted CD8-positive T cells, guiding antigen-specific T cell immune response to eliminate infected or transformed cells (PubMed:2456340, PubMed:2784196, PubMed:1402688, PubMed:7504010, PubMed:9862734, PubMed:10449296, PubMed:12138174, PubMed:12393434, PubMed:15893615, PubMed:17189421, PubMed:19543285, PubMed:21498667, PubMed:24192765, PubMed:7694806, PubMed:24395804, PubMed:28250417). May also present self-peptides derived from the signal sequence of secreted or membrane proteins, although T cells specific for these peptides are usually inactivated to prevent autoreactivity (PubMed:25880248, PubMed:7506728, PubMed:7679507). Both the peptide and the MHC molecule are recognized by TCR, the peptide is responsible for the fine specificity of antigen recognition and MHC residues account for the MHC restriction of T cells (PubMed:12796775, PubMed:18275829, PubMed:19542454, PubMed:28250417). Typically presents intracellular peptide antigens of 8 to 13 amino acids that arise from cytosolic proteolysis via IFNG-induced immunoproteasome or via endopeptidase IDE/insulin-degrading enzyme (PubMed:17189421, PubMed:20364150, PubMed:17079320, PubMed:26929325, PubMed:27049119). Can bind different peptides containing allele-specific binding motifs, which are mainly defined by anchor residues at position 2 and 9 (PubMed:7504010, PubMed:9862734).<ref>PMID:10449296</ref> <ref>PMID:12138174</ref> <ref>PMID:12393434</ref> <ref>PMID:12796775</ref> <ref>PMID:1402688</ref> <ref>PMID:15893615</ref> <ref>PMID:17079320</ref> <ref>PMID:17189421</ref> <ref>PMID:18275829</ref> <ref>PMID:19542454</ref> <ref>PMID:19543285</ref> <ref>PMID:20364150</ref> <ref>PMID:21498667</ref> <ref>PMID:24192765</ref> <ref>PMID:24395804</ref> <ref>PMID:2456340</ref> <ref>PMID:25880248</ref> <ref>PMID:26929325</ref> <ref>PMID:27049119</ref> <ref>PMID:2784196</ref> <ref>PMID:28250417</ref> <ref>PMID:7504010</ref> <ref>PMID:7506728</ref> <ref>PMID:7679507</ref> <ref>PMID:7694806</ref> <ref>PMID:9862734</ref> Allele A01:01: Presents a restricted peptide repertoire including viral epitopes derived from IAV NP/nucleoprotein (CTELKLSDY), IAV PB1/polymerase basic protein 1 (VSDGGPNLY), HAdV-11 capsid L3/hexon protein (LTDLGQNLLY), SARS-CoV-2 3a/ORF3a (FTSDYYQLY) as well as tumor peptide antigens including MAGE1 (EADPTGHSY), MAGEA3 (EVDPIGHLY) and WT1 (TSEKRPFMCAY), all having in common a canonical motif with a negatively charged Asp or Glu residue at position 3 and a Tyr anchor residue at the C-terminus (PubMed:1402688, PubMed:7504010, PubMed:17189421, PubMed:20364150, PubMed:25880248, PubMed:30530481, PubMed:19177349, PubMed:24395804, PubMed:26758806, PubMed:32887977). A number of HLA-A01:01-restricted peptides carry a post-translational modification with oxidation and N-terminal acetylation being the most frequent (PubMed:25880248). Fails to present highly immunogenic peptides from the EBV latent antigens (PubMed:18779413).<ref>PMID:1402688</ref> <ref>PMID:17189421</ref> <ref>PMID:18779413</ref> <ref>PMID:19177349</ref> <ref>PMID:20364150</ref> <ref>PMID:24395804</ref> <ref>PMID:25880248</ref> <ref>PMID:26758806</ref> <ref>PMID:30530481</ref> <ref>PMID:7504010</ref> Allele A02:01: A major allele in human populations, presents immunodominant viral epitopes derived from IAV M/matrix protein 1 (GILGFVFTL), HIV-1 env (TLTSCNTSV), HIV-1 gag-pol (ILKEPVHGV), HTLV-1 Tax (LLFGYPVYV), HBV C/core antigen (FLPSDFFPS), HCMV UL83/pp65 (NLVPMVATV) as well as tumor peptide antigens including MAGEA4 (GVYDGREHTV), WT1 (RMFPNAPYL) and CTAG1A/NY-ESO-1 (SLLMWITQC), all having in common hydrophobic amino acids at position 2 and at the C-terminal anchors.<ref>PMID:11502003</ref> <ref>PMID:12138174</ref> <ref>PMID:12796775</ref> <ref>PMID:17079320</ref> <ref>PMID:18275829</ref> <ref>PMID:19542454</ref> <ref>PMID:20619457</ref> <ref>PMID:22245737</ref> <ref>PMID:26929325</ref> <ref>PMID:2784196</ref> <ref>PMID:28250417</ref> <ref>PMID:7694806</ref> <ref>PMID:7935798</ref> <ref>PMID:8630735</ref> <ref>PMID:8805302</ref> <ref>PMID:8906788</ref> <ref>PMID:9177355</ref> Allele A03:01: Presents viral epitopes derived from IAV NP (ILRGSVAHK), HIV-1 nef (QVPLRPMTYK), HIV-1 gag-pol (AIFQSSMTK), SARS-CoV-2 N/nucleoprotein (KTFPPTEPK) as well as tumor peptide antigens including PMEL (LIYRRRLMK), NODAL (HAYIQSLLK), TRP-2 (RMYNMVPFF), all having in common hydrophobic amino acids at position 2 and Lys or Arg anchor residues at the C-terminus (PubMed:7504010, PubMed:7679507, PubMed:9862734, PubMed:19543285, PubMed:21943705, PubMed:2456340, PubMed:32887977). May also display spliced peptides resulting from the ligation of two separate proteasomal cleavage products that are not contiguous in the parental protein (PubMed:27049119).<ref>PMID:19543285</ref> <ref>PMID:21943705</ref> <ref>PMID:2456340</ref> <ref>PMID:27049119</ref> <ref>PMID:7504010</ref> <ref>PMID:7679507</ref> <ref>PMID:9862734</ref> Allele A11:01: Presents several immunodominant epitopes derived from HIV-1 gag-pol and HHV-4 EBNA4, containing the peptide motif with Val, Ile, Thr, Leu, Tyr or Phe at position 2 and Lys anchor residue at the C-terminus. Important in the control of HIV-1, EBV and HBV infections (PubMed:10449296). Presents an immunodominant epitope derived from SARS-CoV-2 N/nucleoprotein (KTFPPTEPK) (PubMed:32887977).<ref>PMID:10449296</ref> <ref>PMID:32887977</ref> Allele A23:01: Interacts with natural killer (NK) cell receptor KIR3DL1 and may contribute to functional maturation of NK cells and self-nonself discrimination during innate immune response.<ref>PMID:17182537</ref> Allele A24:02: Presents viral epitopes derived from HIV-1 nef (RYPLTFGWCF), EBV lytic- and latent-cycle antigens BRLF1 (TYPVLEEMF), BMLF1 (DYNFVKQLF) and LMP2 (IYVLVMLVL), SARS-CoV nucleocapsid/N (QFKDNVILL), as well as tumor peptide antigens including PRAME (LYVDSLFFL), all sharing a common signature motif, namely an aromatic residue Tyr or Phe at position 2 and a nonhydrophobic anchor residue Phe, Leu or Iso at the C-terminus (PubMed:9047241, PubMed:12393434, PubMed:24192765, PubMed:20844028). Interacts with natural killer (NK) cell receptor KIR3DL1 and may contribute to functional maturation of NK cells and self-nonself discrimination during innate immune response (PubMed:17182537, PubMed:18502829).<ref>PMID:12393434</ref> <ref>PMID:17182537</ref> <ref>PMID:18502829</ref> <ref>PMID:20844028</ref> <ref>PMID:24192765</ref> <ref>PMID:9047241</ref> Allele A26:01: Presents several epitopes derived from HIV-1 gag-pol (EVIPMFSAL, ETKLGKAGY) and env (LVSDGGPNLY), carrying as anchor residues preferentially Glu at position 1, Val or Thr at position 2 and Tyr at the C-terminus.<ref>PMID:15893615</ref> Allele A29:02: Presents peptides having a common motif, namely a Glu residue at position 2 and Tyr or Leu anchor residues at the C-terminus.<ref>PMID:8622959</ref> Allele A32:01: Interacts with natural killer (NK) cell receptor KIR3DL1 and may contribute to functional maturation of NK cells and self-nonself discrimination during innate immune response.<ref>PMID:17182537</ref> Allele A68:01: Presents viral epitopes derived from IAV NP (KTGGPIYKR) and HIV-1 tat (ITKGLGISYGR), having a common signature motif namely, Val or Thr at position 2 and positively charged residues Arg or Lys at the C-terminal anchor.<ref>PMID:1448153</ref> <ref>PMID:1448154</ref> <ref>PMID:2784196</ref> Allele A74:01: Presents immunodominant HIV-1 epitopes derived from gag-pol (GQMVHQAISPR, QIYPGIKVR) and rev (RQIHSISER), carrying an aliphatic residue at position 2 and Arg anchor residue at the C-terminus. May contribute to viral load control in chronic HIV-1 infection.<ref>PMID:21498667</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</div>		</div>
	<div class="pdbe-citations 4qok" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4qok" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Beta-2 microglobulin 3D structures\|Beta-2 microglobulin 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Cole, D K~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Madura, F~~]]	+	[[Category: Cole DK]]
-	[[Category: ~~Rizkallah, P J~~]]	+	[[Category: Madura F]]
-	[[Category: ~~Sewell, A K~~]]	+	[[Category: Rizkallah PJ]]
-	[[Category: ~~Hla]]~~	+	[[Category: Sewell AK]]
-	~~[[Category: Immune system]]~~	+
-	~~[[Category: Immunoglobulin]]~~	+
-	~~[[Category: Melanoma]]~~	+
-	~~[[Category: Tcr~~]]	+

OCA at 08:56, 22 November 2017

OCA — Wed, 22 Nov 2017 08:56:12 GMT

←Older revision		Revision as of 08:56, 22 November 2017
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	<StructureSection load='4qok' size='340' side='right' caption='[[4qok]], [[Resolution\|resolution]] 3.00Å' scene=''>		<StructureSection load='4qok' size='340' side='right' caption='[[4qok]], [[Resolution\|resolution]] 3.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4qok]] is a 5 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QOK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QOK FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4qok]] is a 5 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=4QOK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QOK 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></td></tr>		</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></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3hg1\|3hg1]], [[4jfd\|4jfd]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3hg1\|3hg1]], [[4jfd\|4jfd]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HLA-A, HLAA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), B2M, CDABP0092, HDCMA22P ([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=4qok FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qok OCA], [http://pdbe.org/4qok PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4qok RCSB], [http://www.ebi.ac.uk/pdbsum/4qok PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4qok 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=4qok FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qok OCA], [http://pdbe.org/4qok PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4qok RCSB], [http://www.ebi.ac.uk/pdbsum/4qok PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4qok ProSAT]</span></td></tr>
	</table>		</table>
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	</div>		</div>
	<div class="pdbe-citations 4qok" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4qok" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[Beta-2 microglobulin\|Beta-2 microglobulin]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Cole, D K]]		[[Category: Cole, D K]]
	[[Category: Madura, F]]		[[Category: Madura, F]]

OCA at 17:02, 4 January 2017

OCA — Wed, 04 Jan 2017 17:02:59 GMT

←Older revision		Revision as of 17:02, 4 January 2017
Line 1:		Line 1:
		+
	==Structural basis for ineffective T-cell responses to MHC anchor residue improved heteroclitic peptides==		==Structural basis for ineffective T-cell responses to MHC anchor residue improved heteroclitic peptides==
	<StructureSection load='4qok' size='340' side='right' caption='[[4qok]], [[Resolution\|resolution]] 3.00Å' scene=''>		<StructureSection load='4qok' size='340' side='right' caption='[[4qok]], [[Resolution\|resolution]] 3.00Å' scene=''>
Line 5:		Line 6:
	</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></td></tr>		</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></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3hg1\|3hg1]], [[4jfd\|4jfd]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3hg1\|3hg1]], [[4jfd\|4jfd]]</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=4qok FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qok OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4qok RCSB], [http://www.ebi.ac.uk/pdbsum/4qok 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=4qok FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qok OCA], [http://pdbe.org/4qok PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4qok RCSB], [http://www.ebi.ac.uk/pdbsum/4qok PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4qok ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
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	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 4qok" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Beta-2 microglobulin\|Beta-2 microglobulin]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 12:42, 17 December 2014

OCA — Wed, 17 Dec 2014 12:42:46 GMT

←Older revision		Revision as of 12:42, 17 December 2014
Line 1:		Line 1:
-	'''~~Unreleased~~ structure'''	+	==Structural basis for ineffective T-cell responses to MHC anchor residue improved heteroclitic peptides==
		+	<StructureSection load='4qok' size='340' side='right' caption='[[4qok]], [[Resolution\|resolution]] 3.00Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4qok]] is a 5 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QOK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QOK 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></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3hg1\|3hg1]], [[4jfd\|4jfd]]</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=4qok FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qok OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4qok RCSB], [http://www.ebi.ac.uk/pdbsum/4qok PDBsum]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN]] Defects in B2M are the cause of hypercatabolic hypoproteinemia (HYCATHYP) [MIM:[http://omim.org/entry/241600 241600]]. Affected individuals show marked reduction in serum concentrations of immunoglobulin and albumin, probably due to rapid degradation.<ref>PMID:16549777</ref> Note=Beta-2-microglobulin may adopt the fibrillar configuration of amyloid in certain pathologic states. The capacity to assemble into amyloid fibrils is concentration dependent. Persistently high beta(2)-microglobulin serum levels lead to amyloidosis in patients on long-term hemodialysis.<ref>PMID:3532124</ref> <ref>PMID:1336137</ref> <ref>PMID:7554280</ref> <ref>PMID:4586824</ref> <ref>PMID:8084451</ref> <ref>PMID:12119416</ref> <ref>PMID:12796775</ref> <ref>PMID:16901902</ref> <ref>PMID:16491088</ref> <ref>PMID:17646174</ref> <ref>PMID:18835253</ref> <ref>PMID:18395224</ref> <ref>PMID:19284997</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/1A02_HUMAN 1A02_HUMAN]] Involved in the presentation of foreign antigens to the immune system. [[http://www.uniprot.org/uniprot/MAR1_HUMAN MAR1_HUMAN]] Involved in melanosome biogenesis by ensuring the stability of GPR143. Plays a vital role in the expression, stability, trafficking, and processing of melanocyte protein PMEL, which is critical to the formation of stage II melanosomes.<ref>PMID:15695812</ref> <ref>PMID:19717472</ref> [[http://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN]] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	MHC anchor residue-modified 'heteroclitic' peptides have been used in many cancer vaccine trials and often induce greater immune responses than those by the wildtype peptide. The best-studied system to date is the decamer MART-1/Melan-A26-35 peptide, EAAGIGILTV, where the natural alanine at position 2 has been modified to leucine to improve human leukocyte antigen (HLA)-A*0201 anchoring. The resulting ELAGIGILTV peptide has been used in many studies. We recently showed that T cells primed with the ELAGIGILTV peptide can fail to recognize the natural tumor-expressed peptide efficiently, thereby providing a potential molecular reason for why clinical trials of this peptide have been unsuccessful. Here, we solved the structure of a T-cell receptor (TCR) in complex with wildtype peptide and compared it with its heteroclitic counterpart. The data demonstrate that a suboptimal anchor residue at position 2 enables the TCR to 'pull' the peptide away from the MHC binding groove, facilitating extra contacts with both the peptide and MHC surface. These data explain how a TCR can distinguish between two epitopes and demonstrate how weak MHC anchoring can enable an induced-fit interaction with the TCR. Our findings constitute a novel demonstration of the extreme sensitivity of the TCR to minor alterations in peptide conformation. This article is protected by copyright. All rights reserved.

-	~~The entry 4qok is ON HOLD until Paper Publication~~	+	Structural basis for ineffective T-cell responses to MHC anchor residue-improved 'heteroclitic' peptides.,Madura F, Rizkallah PJ, Holland CJ, Fuller A, Bulek A, Godkin AJ, Schauenburg AJ, Cole DK, Sewell AK Eur J Immunol. 2014 Dec 4. doi: 10.1002/eji.201445114. PMID:25471691<ref>PMID:25471691</ref>

-	~~Authors: Rizkallah~~, P.J., Cole, D.K., Madura, F., Sewell, A.K.	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~Description~~: ~~Structural basis for ineffective T-cell responses to MHC anchor residue improved heteroclitic peptides~~	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Cole, D K]]
		+	[[Category: Madura, F]]
		+	[[Category: Rizkallah, P J]]
		+	[[Category: Sewell, A K]]
		+	[[Category: Hla]]
		+	[[Category: Immune system]]
		+	[[Category: Immunoglobulin]]
		+	[[Category: Melanoma]]
		+	[[Category: Tcr]]

OCA at 09:47, 16 July 2014

OCA — Wed, 16 Jul 2014 09:47:11 GMT

←Older revision		Revision as of 09:47, 16 July 2014
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	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors: Rizkallah, P.J., Cole, D.K., Madura, F., Sewell, A.K.		Authors: Rizkallah, P.J., Cole, D.K., Madura, F., Sewell, A.K.

	Description: Structural basis for ineffective T-cell responses to MHC anchor residue improved heteroclitic peptides		Description: Structural basis for ineffective T-cell responses to MHC anchor residue improved heteroclitic peptides

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

OCA — Wed, 02 Jul 2014 07:25:45 GMT

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

←Older revision

Revision as of 07:25, 2 July 2014

OCA: New page: '''Unreleased structure''' The entry 4qok is ON HOLD Authors: Rizkallah, P.J., Cole, D.K., Madura, F., Sewell, A.K. Description: Structural basis for ineffective T-cell responses to MH...

OCA — Wed, 02 Jul 2014 07:25:43 GMT

New page: '''Unreleased structure''' The entry 4qok is ON HOLD Authors: Rizkallah, P.J., Cole, D.K., Madura, F., Sewell, A.K. Description: Structural basis for ineffective T-cell responses to MH...

New page

'''Unreleased structure'''

The entry 4qok is ON HOLD

Authors: Rizkallah, P.J., Cole, D.K., Madura, F., Sewell, A.K.

Description: Structural basis for ineffective T-cell responses to MHC anchor residue improved heteroclitic peptides