8frt
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==X-ray crystal structure of the N-terminal region from HCMV US11 binding to HLA-A*02:01== | |
| + | <StructureSection load='8frt' size='340' side='right'caption='[[8frt]], [[Resolution|resolution]] 1.80Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8frt]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Human_herpesvirus_5_strain_AD169 Human herpesvirus 5 strain AD169]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8FRT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8FRT 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]] 1.8Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</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=8frt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8frt OCA], [https://pdbe.org/8frt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8frt RCSB], [https://www.ebi.ac.uk/pdbsum/8frt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8frt ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN] Defects in B2M are the cause of hypercatabolic hypoproteinemia (HYCATHYP) [MIM:[https://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 == | ||
| + | [https://www.uniprot.org/uniprot/O78126_HUMAN O78126_HUMAN] [https://www.uniprot.org/uniprot/US11_HCMVA US11_HCMVA] Participates in the inhibition of the host immune response. Redirects newly synthesized major histocompatibility complex (MHC) class I heavy chains via the SEC61 translocon to the cytosol where they undergo proteasome-dependent destruction. In consequence, infected cells are masked for immune recognition by cytotoxic T-lymphocytes.<ref>PMID:15823579</ref> <ref>PMID:19121997</ref> <ref>PMID:8625414</ref> <ref>PMID:8855296</ref> [https://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 == | ||
| + | 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 8frt" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Human herpesvirus 5 strain AD169]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Berry R]] | ||
| + | [[Category: Rossjohn J]] | ||
| + | [[Category: Watson GM]] | ||
Current revision
X-ray crystal structure of the N-terminal region from HCMV US11 binding to HLA-A*02:01
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