9opr

TMPRSS2 S441A in complex with the H1H7 Fab and anti-kappa light chain nanobody

spinqualitylabelsall models 9opr, resolution 3.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9opr is a 4 chain structure with sequence from Homo sapiens and Lama glama. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.2Å Ligands: NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function 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] (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. SUMO_YEAST Ubiquitin-like protein that can be covalently attached to proteins as a monomer or a lysine-linked polymer (PubMed:9312010). Sumoylation, the attachment of SUMO to target proteins, regulates multiple cellular events (By similarity).[UniProtKB:O13351] Publication Abstract from PubMed The protease TMPRSS2 facilitates coronavirus infections, yet its mechanism of viral glycoprotein recognition remains unclear. Here we show that, following ACE2 engagement of the SARS-CoV-2 spike (S) inducing the early fusion intermediate conformation (E-FIC), TMPRSS2 cleaves the R815 S(2)' site and promotes fusogenic conformational changes leading to viral entry. We unveil TMPRSS2 recognition of S(2)', identify key residues modulating binding specificity and demonstrate that S(2)' site-directed broadly neutralizing antibodies target E-FIC and inhibit viral entry by blocking TMPRSS2 access. We computationally designed stabilized E-FIC as a vaccine candidate, overcoming the transient nature of this state. We describe a TMPRSS2-directed monoclonal antibody inhibiting several coronaviruses, including SARS-CoV-2 variants and protecting mice against SARS-CoV-2 challenge. These results outline the mechanistic role of TMPRSS2 and S(2)' site-directed antibodies in coronavirus entry. TMPRSS2-mediated coronavirus spike activation and inhibition.,McCallum M, Case JB, Brown JT, Park YJ, Lee J, Sutherland E, Aggarwal A, Gibson C, Lempp FA, Stewart C, Tortorici MA, Sanapala S, Low JS, Asarnow D, Bohan D, Dellota E Jr, Merz B, Chawla B, Kar S, Lanzavecchia A, Sallusto F, Riley NM, Turville S, Purcell L, Diamond MS, Veesler D Nat Struct Mol Biol. 2026 Apr 28. doi: 10.1038/s41594-026-01801-y. PMID:42050172 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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