8Y0Q
Complex of FMDV O/18074 and inter-serotype broadly neutralizing antibodies pOA-2
Summary for 8Y0Q
| Entry DOI | 10.2210/pdb8y0q/pdb |
| Related | 8Y0R |
| EMDB information | 38814 |
| Descriptor | VP1 of capsid protein, VP2 of capsid protein, VP3 of capsid protein, ... (6 entities in total) |
| Functional Keywords | foot-and-mouth disease virus o, sus scrofa, virus/immune system, virus-immune system complex |
| Biological source | Sus scrofa More |
| Total number of polymer chains | 6 |
| Total formula weight | 106095.60 |
| Authors | |
| Primary citation | Li, F.,Wu, S.,Lv, L.,Huang, S.,Zhang, Z.,Zerang, Z.,Li, P.,Cao, Y.,Bao, H.,Sun, P.,Bai, X.,He, Y.,Fu, Y.,Yuan, H.,Ma, X.,Zhao, Z.,Zhang, J.,Wang, J.,Wang, T.,Li, D.,Zhang, Q.,He, J.,Liu, Z.,Lu, Z.,Lei, D.,Li, K. Discovery, recognized antigenic structures, and evolution of cross-serotype broadly neutralizing antibodies from porcine B-cell repertoires against foot-and-mouth disease virus. Plos Pathog., 20:e1012623-e1012623, 2024 Cited by PubMed Abstract: It is a great challenge to isolate the broadly neutralizing antibodies (bnAbs) against foot-and-mouth disease virus (FMDV) due to its existence as seven distinct serotypes without cross-protection. Here, by vaccination of pig with FMDV serotypes O and A whole virus antigens, we obtained 10 bnAbs against serotypes O, A and/or Asia1 by dissecting 216 common clonotypes of two serotypes O and A specific porcine B-cell receptor (BCR) gene repertoires containing total 12720 B cell clones, indicating the induction of cross-serotype bnAbs after sequential vaccination with serotypes O and A antigens. The majority of porcine bnAbs (9/10) were derived from terminally differentiated B cells of different clonal lineages, which convergently targeted the conserved "RGDL" motif on structural protein VP1 of FMDV by mimicking receptor recognition to inhibit viral attachment to cells. Cryo-EM complex structures revealed that the other bnAb pOA-2 specifically targets a novel inter-pentamer antigen structure surrounding the viral three-fold axis, with a highly conserved determinant at residue 68 on VP2. This unique binding pattern enabled cross-serotype neutralization by destabilizing the viral particle. The evolutionary analysis of pOA-2 demonstrated its origin from an intermediate B-cell, emphasizing the crucial role of somatic hypermutations (SHMs) in balancing the breadth and potency of neutralization. However, excessive SHMs may deviate from the trajectory of broad neutralization. This study provides a strategy to uncover bnAbs against highly mutable pathogens and the cross-serotype antigenic structures to explore broadly protective FMDV vaccine. PubMed: 39405339DOI: 10.1371/journal.ppat.1012623 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.44 Å) |
Structure validation
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