View source for 8cmc


==Human Leukocyte Antigen class II allotype DR1 presenting SARS-CoV-2 Spike peptide S511-530==
<StructureSection load='8cmc' size='340' side='right'caption='[[8cmc]], [[Resolution|resolution]] 1.42&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8cmc]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Severe_acute_respiratory_syndrome_coronavirus_2 Severe acute respiratory syndrome coronavirus 2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8CMC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8CMC 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]] 1.42&#8491;</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>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=8cmc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8cmc OCA], [https://pdbe.org/8cmc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8cmc RCSB], [https://www.ebi.ac.uk/pdbsum/8cmc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8cmc ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
CD4(+) T cells recognize a broad range of peptide epitopes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which contribute to immune memory and limit COVID-19 disease. We demonstrate that the immunogenicity of SARS-CoV-2 peptides, in the context of the model allotype HLA-DR1, does not correlate with their binding affinity to the HLA heterodimer. Analyzing six epitopes, some with very low binding affinity, we solve X-ray crystallographic structures of each bound to HLA-DR1. Further structural definitions reveal the precise molecular impact of viral variant mutations on epitope presentation. Omicron escaped ancestral SARS-CoV-2 immunity to two epitopes through two distinct mechanisms: (1) mutations to TCR-facing epitope positions and (2) a mechanism whereby a single amino acid substitution caused a register shift within the HLA binding groove, completely altering the peptide-HLA structure. This HLA-II-specific paradigm of immune escape highlights how CD4(+) T cell memory is finely poised at the level of peptide-HLA-II presentation.

Structural definition of HLA class II-presented SARS-CoV-2 epitopes reveals a mechanism to escape pre-existing CD4(+) T cell immunity.,Chen Y, Mason GH, Scourfield DO, Greenshields-Watson A, Haigh TA, Sewell AK, Long HM, Gallimore AM, Rizkallah P, MacLachlan BJ, Godkin A Cell Rep. 2023 Aug 29;42(8):112827. doi: 10.1016/j.celrep.2023.112827. Epub 2023 , Jul 19. PMID:37471227<ref>PMID:37471227</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8cmc" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Severe acute respiratory syndrome coronavirus 2]]
[[Category: Godkin AJ]]
[[Category: MacLachlan BJ]]
[[Category: Mason GH]]
[[Category: Rizkallah PJ]]
[[Category: Sourfield DO]]