8s0n
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of the TMPRSS2 zymogen in complex with the nanobody A07== | |
| + | <StructureSection load='8s0n' size='340' side='right'caption='[[8s0n]], [[Resolution|resolution]] 2.30Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8s0n]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Vicugna_pacos Vicugna pacos]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8S0N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8S0N 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]] 2.3Å</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=8s0n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8s0n OCA], [https://pdbe.org/8s0n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8s0n RCSB], [https://www.ebi.ac.uk/pdbsum/8s0n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8s0n ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [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> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The human seasonal coronavirus HKU1-CoV, which causes common colds worldwide, relies on the sequential binding to surface glycans and transmembrane serine protease 2 (TMPRSS2) for entry into target cells. TMPRSS2 is synthesized as a zymogen that undergoes autolytic activation to process its substrates. Several respiratory viruses, in particular coronaviruses, use TMPRSS2 for proteolytic priming of their surface spike protein to drive membrane fusion upon receptor binding. We describe the crystal structure of the HKU1-CoV receptor binding domain in complex with TMPRSS2, showing that it recognizes residues lining the catalytic groove. Combined mutagenesis of interface residues and comparison across species highlight positions 417 and 469 as determinants of HKU1-CoV host tropism. The structure of a receptor-blocking nanobody in complex with zymogen or activated TMPRSS2 further provides the structural basis of TMPRSS2 activating conformational change, which alters loops recognized by HKU1-CoV and dramatically increases binding affinity. | ||
| - | + | Structural basis of TMPRSS2 zymogen activation and recognition by the HKU1 seasonal coronavirus.,Fernandez I, Saunders N, Duquerroy S, Bolland WH, Arbabian A, Baquero E, Blanc C, Lafaye P, Haouz A, Buchrieser J, Schwartz O, Rey FA Cell. 2024 Aug 8;187(16):4246-4260.e16. doi: 10.1016/j.cell.2024.06.007. Epub , 2024 Jul 3. PMID:38964326<ref>PMID:38964326</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 8s0n" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Vicugna pacos]] | ||
| + | [[Category: Duquerroy S]] | ||
| + | [[Category: Fernandez I]] | ||
| + | [[Category: Rey F]] | ||
Current revision
Crystal structure of the TMPRSS2 zymogen in complex with the nanobody A07
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