View source for 6vm8


==SILv44 T cell receptor bound to HLA-A2 presenting gp100T2M peptide (IMDQVPFSV)==
<StructureSection load='6vm8' size='340' side='right'caption='[[6vm8]], [[Resolution|resolution]] 2.41&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6vm8]] 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=6VM8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VM8 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.41&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FLC:CITRATE+ANION'>FLC</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=6vm8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vm8 OCA], [https://pdbe.org/6vm8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vm8 RCSB], [https://www.ebi.ac.uk/pdbsum/6vm8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vm8 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A0A140T913_HUMAN A0A140T913_HUMAN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Presentation of peptides by class I MHC proteins underlies T cell immune responses to pathogens and cancer. The association between peptide binding affinity and immunogenicity has led to the engineering of modified peptides with improved MHC binding, with the hope that these peptides would be useful for eliciting cross-reactive immune responses directed toward their weak binding, unmodified counterparts. Increasing evidence, however, indicates that T cell receptors (TCRs) can perceive such anchor-modified peptides differently than wild-type (WT) peptides, although the scope of discrimination is unclear. We show here that even modifications at primary anchors that have no discernible structural impact can lead to substantially stronger or weaker T cell recognition depending on the TCR. Surprisingly, the effect of peptide anchor modification can be sensed by a TCR at regions distant from the site of modification, indicating a through-protein mechanism in which the anchor residue serves as an allosteric modulator for TCR binding. Our findings emphasize caution in the use and interpretation of results from anchor-modified peptides and have implications for how anchor modifications are accounted for in other circumstances, such as predicting the immunogenicity of tumor neoantigens. Our data also highlight an important need to better understand the highly tunable dynamic nature of class I MHC proteins and the impact this has on various forms of immune recognition.

Structurally silent peptide anchor modifications allosterically modulate T cell recognition in a receptor-dependent manner.,Smith AR, Alonso JA, Ayres CM, Singh NK, Hellman LM, Baker BM Proc Natl Acad Sci U S A. 2021 Jan 26;118(4):e2018125118. doi: , 10.1073/pnas.2018125118. PMID:33468649<ref>PMID:33468649</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6vm8" style="background-color:#fffaf0;"></div>

==See Also==
*[[Beta-2 microglobulin 3D structures|Beta-2 microglobulin 3D structures]]
*[[MHC 3D structures|MHC 3D structures]]
*[[MHC I 3D structures|MHC I 3D structures]]
*[[T-cell receptor 3D structures|T-cell receptor 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Baker BM]]
[[Category: Smith AR]]