8I5L
Crystal structure of P domain from norovirus GI.4 capsid protein in complex with broad specificity antibody single-chain Fv fragment CV-2F5.
Summary for 8I5L
| Entry DOI | 10.2210/pdb8i5l/pdb |
| Descriptor | Capsid protein, scFv fragment (3 entities in total) |
| Functional Keywords | norovirus, p-domain, capsid, viral protein, single-chain fv fragment, antibody-protein complex |
| Biological source | Chiba virus More |
| Total number of polymer chains | 5 |
| Total formula weight | 156357.58 |
| Authors | Kato-Murayama, M.,Murayama, K.,Shirouzu, M. (deposition date: 2023-01-26, release date: 2024-01-31, Last modification date: 2024-10-16) |
| Primary citation | Kimura-Someya, T.,Katsura, K.,Kato-Murayama, M.,Hosaka, T.,Uchikubo-Kamo, T.,Ihara, K.,Hanada, K.,Sato, S.,Murayama, K.,Kataoka, M.,Shirouzu, M.,Someya, Y. Structural analyses of the GI.4 norovirus by cryo-electron microscopy and X-ray crystallography revealing binding sites for human monoclonal antibodies. J.Virol., 98:e0019724-e0019724, 2024 Cited by PubMed Abstract: Noroviruses are major causative agents of acute nonbacterial gastroenteritis in humans. There are neither antiviral therapeutic agents nor vaccines for noroviruses at this time. To evaluate the potential usefulness of two previously isolated human monoclonal antibody fragments, CV-1A1 and CV-2F5, we first conducted a single-particle analysis to determine the cryo-electron microscopy structure of virus-like particles (VLPs) from the genogroup I genotype 4 (GI.4) Chiba strain uniformly coated with CV-1A1 fragments. The results revealed that the GI.4-specific CV-1A1 antibody bound to the P2 subdomain, in which amino acids are less conserved and variable. Interestingly, a part of the CV-1A1 intrudes into the histo-blood group antigen-binding site, suggesting that this antibody might exert neutralizing activity. Next, we determined the crystal structure of the protruding (P) domain of the capsid protein in the complex form with the CV-2F5 antibody fragment. Consistent with the cross-reactivity, the CV-2F5 bound to the P1 subdomain, which is rich in amino acids conserved among the GI strains, and moreover induced a disruption of Chiba VLPs. These results suggest that the broadly reactive CV-2F5 antibody can be used as both a universal detection reagent and an antiviral drug for GI noroviruses. PubMed: 38593321DOI: 10.1128/jvi.00197-24 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.7 Å) |
Structure validation
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