7EO0
FOOT AND MOUTH DISEASE VIRUS O/TIBET/99-BOUND THE SINGLE CHAIN FRAGMEN ANTIBODY C4
Summary for 7EO0
| Entry DOI | 10.2210/pdb7eo0/pdb |
| EMDB information | 31223 |
| Descriptor | O/TIBET/99 VP1, O/TIBET/99 VP2, O/TIBET/99 VP3, ... (6 entities in total) |
| Functional Keywords | foot and mouth disease virus, fmdv, virus |
| Biological source | Bos taurus (Bovine) More |
| Total number of polymer chains | 6 |
| Total formula weight | 107226.51 |
| Authors | |
| Primary citation | Li, K.,He, Y.,Wang, L.,Li, P.,Wang, S.,Sun, P.,Bao, H.,Cao, Y.,Liu, X.,Zhu, G.,Song, Y.,Bai, X.,Ma, X.,Fu, Y.,Yuan, H.,Zhang, J.,Wang, J.,Chen, Y.,Li, D.,Lou, Z.,Liu, Z.,Lu, Z. Two Cross-Protective Antigen Sites on Foot-and-Mouth Disease Virus Serotype O Structurally Revealed by Broadly Neutralizing Antibodies from Cattle. J.Virol., 95:e0088121-e0088121, 2021 Cited by PubMed Abstract: Foot-and-mouth disease virus (FMDV) is a highly contagious virus that infects cloven-hoofed animals. Neutralizing antibodies play critical roles in antiviral infection. Although five known antigen sites that induce neutralizing antibodies have been defined, studies on cross-protective antigen sites are still scarce. We mapped two cross-protective antigen sites using 13 bovine-derived broadly neutralizing monoclonal antibodies (bnAbs) capable of neutralizing 4 lineages within 3 topotypes of FMDV serotype O. One antigen site was formed by a novel cluster of VP3-focused epitopes recognized by bnAb C4 and C4-like antibodies. The cryo-electron microscopy (cryo-EM) structure of the FMDV-OTi (O/Tibet/99)-C4 complex showed close contact with VP3 and a novel interprotomer antigen epitope around the icosahedral 3-fold axis of the FMDV particle, which is far beyond the known antigen site 4. The key determinants of the neutralizing function of C4 and C4-like antibodies on the capsid were βB (T65), the B-C loop (T68), the E-F loop (E131 and K134), and the H-I loop (G196), revealing a novel antigen site on VP3. The other antigen site comprised two group epitopes on VP2 recognized by 9 bnAbs (B57, B73, B77, B82, F28, F145, F150, E46, and E54), which belong to the known antigen site 2 of FMDV serotype O. Notably, bnAb C4 potently promoted FMDV RNA release in response to damage to viral particles, suggesting that the targeted epitope contains a trigger mechanism for particle disassembly. This study revealed two cross-protective antigen sites that can elicit cross-reactive neutralizing antibodies in cattle and provided new structural information for the design of a broad-spectrum molecular vaccine against FMDV serotype O. FMDV is the causative agent of foot-and-mouth disease (FMD), which is one of the most contagious and economically devastating diseases of domestic animals. The antigenic structure of FMDV serotype O is rather complicated, especially for those sites that can elicit a cross-protective neutralizing antibody response. Monoclonal neutralization antibodies provide both crucial defense components against FMDV infection and valuable tools for fine analysis of the antigenic structure. In this study, we found a cluster of novel VP3-focused epitopes using 13 bnAbs against FMDV serotype O from natural host cattle, which revealed two cross-protective antigen sites on VP2 and VP3. Antibody C4 targeting this novel epitope potently promoted viral particle disassembly and RNA release before infection, which may indicate a vulnerable region of FMDV. This study reveals new structural information about cross-protective antigen sites of FMDV serotype O, providing valuable and strong support for future research on broad-spectrum vaccines against FMD. PubMed: 34406868DOI: 10.1128/JVI.00881-21 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.75 Å) |
Structure validation
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