8y8a

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Current revision (12:25, 17 July 2024) (edit) (undo)
 
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'''Unreleased structure'''
 
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The entry 8y8a is ON HOLD until Paper Publication
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==Structure of HCoV-HKU1C spike in the functionally anchored-3up conformation with 3TMPRSS2==
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<StructureSection load='8y8a' size='340' side='right'caption='[[8y8a]], [[Resolution|resolution]] 3.19&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[8y8a]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Human_coronavirus_HKU1_(isolate_N5) Human coronavirus HKU1 (isolate N5)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8Y8A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8Y8A FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.19&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8y8a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8y8a OCA], [https://pdbe.org/8y8a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8y8a RCSB], [https://www.ebi.ac.uk/pdbsum/8y8a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8y8a ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/TMPS2_HUMAN TMPS2_HUMAN] Plasma membrane-anchored serine protease that participates in proteolytic cascades of relevance for the normal physiologic function of the prostate (PubMed:25122198). Androgen-induced TMPRSS2 activates several substrates that include pro-hepatocyte growth factor/HGF, the protease activated receptor-2/F2RL1 or matriptase/ST14 leading to extracellular matrix disruption and metastasis of prostate cancer cells (PubMed:15537383, PubMed:26018085, PubMed:25122198). In addition, activates trigeminal neurons and contribute to both spontaneous pain and mechanical allodynia (By similarity).[UniProtKB:Q9JIQ8]<ref>PMID:15537383</ref> <ref>PMID:25122198</ref> <ref>PMID:26018085</ref> (Microbial infection) Facilitates human coronaviruses SARS-CoV and SARS-CoV-2 infections via two independent mechanisms, proteolytic cleavage of ACE2 receptor which promotes viral uptake, and cleavage of coronavirus spike glycoproteins which activates the glycoprotein for host cell entry (PubMed:24227843, PubMed:32142651, PubMed:32404436). Proteolytically cleaves and activates the spike glycoproteins of human coronavirus 229E (HCoV-229E) and human coronavirus EMC (HCoV-EMC) and the fusion glycoproteins F0 of Sendai virus (SeV), human metapneumovirus (HMPV), human parainfluenza 1, 2, 3, 4a and 4b viruses (HPIV). Essential for spread and pathogenesis of influenza A virus (strains H1N1, H3N2 and H7N9); involved in proteolytic cleavage and activation of hemagglutinin (HA) protein which is essential for viral infectivity.<ref>PMID:21068237</ref> <ref>PMID:21325420</ref> <ref>PMID:23536651</ref> <ref>PMID:23966399</ref> <ref>PMID:24027332</ref> <ref>PMID:24227843</ref> <ref>PMID:32142651</ref> <ref>PMID:32404436</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The entry of coronaviruses is initiated by spike recognition of host cellular receptors, involving proteinaceous and/or glycan receptors. Recently, TMPRSS2 was identified as the proteinaceous receptor for HCoV-HKU1 alongside sialoglycan as a glycan receptor. However, the underlying mechanisms for viral entry remain unknown. Here, we investigated the HCoV-HKU1C spike in the inactive, glycan-activated, and functionally anchored states, revealing that sialoglycan binding induces a conformational change of the NTD and promotes the neighboring RBD of the spike to open for TMPRSS2 recognition, exhibiting a synergistic mechanism for the entry of HCoV-HKU1. The RBD of HCoV-HKU1 features an insertion subdomain that recognizes TMPRSS2 through three previously undiscovered interfaces. Furthermore, structural investigation of HCoV-HKU1A in combination with mutagenesis and binding assays confirms a conserved receptor recognition pattern adopted by HCoV-HKU1. These studies advance our understanding of the complex viral-host interactions during entry, laying the groundwork for developing new therapeutics against coronavirus-associated diseases.
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Authors:
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TMPRSS2 and glycan receptors synergistically facilitate coronavirus entry.,Wang H, Liu X, Zhang X, Zhao Z, Lu Y, Pu D, Zhang Z, Chen J, Wang Y, Li M, Dong X, Duan Y, He Y, Mao Q, Guo H, Sun H, Zhou Y, Yang Q, Gao Y, Yang X, Cao H, Guddat L, Sun L, Rao Z, Yang H Cell. 2024 Jun 21:S0092-8674(24)00656-1. doi: 10.1016/j.cell.2024.06.016. PMID:38964329<ref>PMID:38964329</ref>
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Description:
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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<div class="pdbe-citations 8y8a" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Liu XC]]
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[[Category: Lu YC]]
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[[Category: Sun L]]
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[[Category: Wang HF]]
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[[Category: Yang HT]]
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[[Category: Zhang X]]

Current revision

Structure of HCoV-HKU1C spike in the functionally anchored-3up conformation with 3TMPRSS2

PDB ID 8y8a

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