8fu4: Difference between revisions
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==HCMV US11 peptide binding to HLA-A*02:01== | |||
<StructureSection load='8fu4' size='340' side='right'caption='[[8fu4]], [[Resolution|resolution]] 1.60Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8fu4]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8FU4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8FU4 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]] 1.6Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CD:CADMIUM+ION'>CD</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</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=8fu4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8fu4 OCA], [https://pdbe.org/8fu4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8fu4 RCSB], [https://www.ebi.ac.uk/pdbsum/8fu4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8fu4 ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Recurrent, ancient arms races between viruses and hosts have shaped both host immunological defense strategies as well as viral countermeasures. One such battle is waged by the glycoprotein US11 encoded by the persisting human cytomegalovirus. US11 mediates degradation of major histocompatibility class I (MHC-I) molecules to prevent CD8+ T-cell activation. Here, we studied the consequences of the arms race between US11 and primate MHC-A proteins, leading us to uncover a tit-for-tat coevolution and its impact on MHC-A diversification. We found that US11 spurred MHC-A adaptation to evade viral antagonism: In an ancestor of great apes, the MHC-A A2 lineage acquired a Pro184Ala mutation, which confers resistance against the ancestral US11 targeting strategy. In response, US11 deployed a unique low-complexity region (LCR), which exploits the MHC-I peptide loading complex to target the MHC-A2 peptide-binding groove. In addition, the global spread of the human HLA-A*02 allelic family prompted US11 to employ a superior LCR strategy with an optimally fitting peptide mimetic that specifically antagonizes HLA-A*02. Thus, despite cytomegaloviruses low pathogenic potential, the increasing commitment of US11 to MHC-A has significantly promoted diversification of MHC-A in hominids. | |||
Diverse cytomegalovirus US11 antagonism and MHC-A evasion strategies reveal a tit-for-tat coevolutionary arms race in hominids.,Zimmermann C, Watson GM, Bauersfeld L, Berry R, Ciblis B, Lan H, Gerke C, Oberhardt V, Fuchs J, Hofmann M, Freund C, Rossjohn J, Momburg F, Hengel H, Halenius A Proc Natl Acad Sci U S A. 2024 Feb 27;121(9):e2315985121. doi: , 10.1073/pnas.2315985121. Epub 2024 Feb 20. PMID:38377192<ref>PMID:38377192</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 8fu4" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Synthetic construct]] | |||
[[Category: Berry R]] | |||
[[Category: Littler DR]] | |||
[[Category: Rossjohn J]] | |||
[[Category: Watson GM]] | |||
Latest revision as of 12:38, 17 October 2024
HCMV US11 peptide binding to HLA-A*02:01HCMV US11 peptide binding to HLA-A*02:01
Structural highlights
Publication Abstract from PubMedRecurrent, ancient arms races between viruses and hosts have shaped both host immunological defense strategies as well as viral countermeasures. One such battle is waged by the glycoprotein US11 encoded by the persisting human cytomegalovirus. US11 mediates degradation of major histocompatibility class I (MHC-I) molecules to prevent CD8+ T-cell activation. Here, we studied the consequences of the arms race between US11 and primate MHC-A proteins, leading us to uncover a tit-for-tat coevolution and its impact on MHC-A diversification. We found that US11 spurred MHC-A adaptation to evade viral antagonism: In an ancestor of great apes, the MHC-A A2 lineage acquired a Pro184Ala mutation, which confers resistance against the ancestral US11 targeting strategy. In response, US11 deployed a unique low-complexity region (LCR), which exploits the MHC-I peptide loading complex to target the MHC-A2 peptide-binding groove. In addition, the global spread of the human HLA-A*02 allelic family prompted US11 to employ a superior LCR strategy with an optimally fitting peptide mimetic that specifically antagonizes HLA-A*02. Thus, despite cytomegaloviruses low pathogenic potential, the increasing commitment of US11 to MHC-A has significantly promoted diversification of MHC-A in hominids. Diverse cytomegalovirus US11 antagonism and MHC-A evasion strategies reveal a tit-for-tat coevolutionary arms race in hominids.,Zimmermann C, Watson GM, Bauersfeld L, Berry R, Ciblis B, Lan H, Gerke C, Oberhardt V, Fuchs J, Hofmann M, Freund C, Rossjohn J, Momburg F, Hengel H, Halenius A Proc Natl Acad Sci U S A. 2024 Feb 27;121(9):e2315985121. doi: , 10.1073/pnas.2315985121. Epub 2024 Feb 20. PMID:38377192[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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