8V62
Structure of the Human Respirovirus 3 Fusion Protein Bound to Camelid Nanobodies 1D10 and 4C06
Summary for 8V62
| Entry DOI | 10.2210/pdb8v62/pdb |
| Related | 8V5K |
| EMDB information | 42983 42987 |
| Descriptor | Fusion glycoprotein F0, Camelid nanobody 1D10, Camelid nanobody 4C06 (3 entities in total) |
| Functional Keywords | viral fusion protein, camelid nanobodies, viral glycoprotein, membrane fusion, viral protein, viral protein-immune system complex, viral protein/immune system |
| Biological source | Human respirovirus 3 More |
| Total number of polymer chains | 9 |
| Total formula weight | 246783.74 |
| Authors | Johnson, N.J.,Ramamohan, A.R.,McLellan, J.S. (deposition date: 2023-12-01, release date: 2024-05-22, Last modification date: 2024-10-16) |
| Primary citation | Johnson, N.V.,van Scherpenzeel, R.C.,Bakkers, M.J.G.,Ramamohan, A.R.,van Overveld, D.,Le, L.,Langedijk, J.P.M.,Kolkman, J.A.,McLellan, J.S. Structural basis for potent neutralization of human respirovirus type 3 by protective single-domain camelid antibodies. Nat Commun, 15:5458-5458, 2024 Cited by PubMed Abstract: Respirovirus 3 is a leading cause of severe acute respiratory infections in vulnerable human populations. Entry into host cells is facilitated by the attachment glycoprotein and the fusion glycoprotein (F). Because of its crucial role, F represents an attractive therapeutic target. Here, we identify 13 F-directed heavy-chain-only antibody fragments that neutralize recombinant respirovirus 3. High-resolution cryo-EM structures of antibody fragments bound to the prefusion conformation of F reveal three distinct, previously uncharacterized epitopes. All three antibody fragments bind quaternary epitopes on F, suggesting mechanisms for neutralization that may include stabilization of the prefusion conformation. Studies in cotton rats demonstrate the prophylactic efficacy of these antibody fragments in reducing viral load in the lungs and nasal passages. These data highlight the potential of heavy-chain-only antibody fragments as effective interventions against respirovirus 3 infection and identify neutralizing epitopes that can be targeted for therapeutic development. PubMed: 38937429DOI: 10.1038/s41467-024-49757-1 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.4 Å) |
Structure validation
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