11HK
SARS-CoV-2 spike S2 trimer stabilized in the early fusion intermediate conformation (E-FICs-v3) bound to the VN01H1 Fab (Fab local refinement)
Summary for 11HK
| Entry DOI | 10.2210/pdb11hk/pdb |
| Related | 11HL |
| EMDB information | 75694 75721 |
| Descriptor | E-FICS-v3, Heavy chain of VN01H1 Fab, Light chain of VN01H1 Fab, ... (5 entities in total) |
| Functional Keywords | s2prime, coronavirus, sars-cov-2, spike, fusion, entry, antiviral, structural genomics, seattle structural genomics center for infectious disease, ssgcid, viral protein-hydrolase complex, vn01h1, viral protein |
| Biological source | Saccharomyces cerevisiae S288C More |
| Total number of polymer chains | 9 |
| Total formula weight | 347323.83 |
| Authors | McCallum, M.,Seattle Structural Genomics Center for Infectious Disease (SSGCID),Veesler, D. (deposition date: 2026-02-24, release date: 2026-05-13) |
| Primary citation | McCallum, M.,Case, J.B.,Brown, J.T.,Park, Y.J.,Lee, J.,Sutherland, E.,Aggarwal, A.,Gibson, C.,Lempp, F.A.,Stewart, C.,Tortorici, M.A.,Sanapala, S.,Low, J.S.,Asarnow, D.,Bohan, D.,Dellota Jr., E.,Merz, B.,Chawla, B.,Kar, S.,Lanzavecchia, A.,Sallusto, F.,Riley, N.M.,Turville, S.,Purcell, L.,Diamond, M.S.,Veesler, D. TMPRSS2-mediated coronavirus spike activation and inhibition. Nat.Struct.Mol.Biol., 2026 Cited by PubMed Abstract: 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' site and promotes fusogenic conformational changes leading to viral entry. We unveil TMPRSS2 recognition of S', identify key residues modulating binding specificity and demonstrate that S' 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' site-directed antibodies in coronavirus entry. PubMed: 42050172DOI: 10.1038/s41594-026-01801-y PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.7 Å) |
Structure validation
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