8VGT
Structure of the HKU1 RBD bound to the human TMPRSS2 receptor
Summary for 8VGT
| Entry DOI | 10.2210/pdb8vgt/pdb |
| EMDB information | 43224 |
| Descriptor | Spike protein S1, Transmembrane protease serine 2, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total) |
| Functional Keywords | spike glycoprotein, fusion protein, structural genomics, seattle structural genomics center for infectious disease, ssgcid, inhibitor, viral protein |
| Biological source | Human coronavirus HKU1 (isolate N1) More |
| Total number of polymer chains | 2 |
| Total formula weight | 84641.81 |
| Authors | Park, Y.J.,Seattle Structural Genomics Center for Infectious Disease (SSGCID),Veesler, D. (deposition date: 2023-12-27, release date: 2024-03-06, Last modification date: 2024-10-16) |
| Primary citation | McCallum, M.,Park, Y.J.,Stewart, C.,Sprouse, K.R.,Addetia, A.,Brown, J.,Tortorici, M.A.,Gibson, C.,Wong, E.,Ieven, M.,Telenti, A.,Veesler, D. Human coronavirus HKU1 recognition of the TMPRSS2 host receptor. Cell, 187:4231-, 2024 Cited by PubMed Abstract: The human coronavirus HKU1 spike (S) glycoprotein engages host cell surface sialoglycans and transmembrane protease serine 2 (TMPRSS2) to initiate infection. The molecular basis of HKU1 binding to TMPRSS2 and determinants of host receptor tropism remain elusive. We designed an active human TMPRSS2 construct enabling high-yield recombinant production in human cells of this key therapeutic target. We determined a cryo-electron microscopy structure of the HKU1 RBD bound to human TMPRSS2, providing a blueprint of the interactions supporting viral entry and explaining the specificity for TMPRSS2 among orthologous proteases. We identified TMPRSS2 orthologs from five mammalian orders promoting HKU1 S-mediated entry into cells along with key residues governing host receptor usage. Our data show that the TMPRSS2 binding motif is a site of vulnerability to neutralizing antibodies and suggest that HKU1 uses S conformational masking and glycan shielding to balance immune evasion and receptor engagement. PubMed: 38964328DOI: 10.1016/j.cell.2024.06.006 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.9 Å) |
Structure validation
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