4qok: Difference between revisions

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'''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]] 3.00&Aring;' 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&reg;/PubMed&reg;, 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]]
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