8GSP

Complex of FMDV A/WH/CHA/09 and bovine neutralizing scFv antibody W2

Summary for 8GSP

• Entry DOI: 10.2210/pdb8gsp/pdb
• EMDB information: 34238
• Descriptor: A/WH/CHA/09 VP1, A/WH/CHA/09 VP2, A/WH/CHA/09 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: 107739.65

Authors

He, Y.,Li, K. (deposition date: 2022-09-06, release date: 2023-10-11, Last modification date: 2024-11-13)

Primary citation

Li, K.,He, Y.,Wang, L.,Li, P.,Bao, H.,Huang, S.,Zhou, S.,Zhu, G.,Song, Y.,Li, Y.,Wang, S.,Zhang, Q.,Sun, P.,Bai, X.,Zhao, Z.,Lou, Z.,Cao, Y.,Lu, Z.,Liu, Z.
Conserved antigen structures and antibody-driven variations on foot-and-mouth disease virus serotype A revealed by bovine neutralizing monoclonal antibodies.
Plos Pathog., 19:e1011811-e1011811, 2023

PubMed Abstract: Foot-and-mouth disease virus (FMDV) serotype A is antigenically most variable within serotypes. The structures of conserved and variable antigenic sites were not well resolved. Here, a historical A/AF72 strain from A22 lineage and a latest A/GDMM/2013 strain from G2 genotype of Sea97 lineage were respectively used as bait antigen to screen single B cell antibodies from bovine sequentially vaccinated with A/WH/CHA/09 (G1 genotype of Sea97 lineage), A/GDMM/2013 and A/AF72 antigens. Total of 39 strain-specific and 5 broad neutralizing antibodies (bnAbs) were isolated and characterized. Two conserved antigenic sites were revealed by the Cryo-EM structures of FMDV serotype A with two bnAbs W2 and W125. The contact sites with both VH and VL of W125 were closely around icosahedral threefold axis and covered the B-C, E-F, and H-I loops on VP2 and the B-B knob and H-I loop on VP3; while contact sites with only VH of W2 concentrated on B-B knob, B-C and E-F loops on VP3 scattering around the three-fold axis of viral particle. Additional highly conserved epitopes also involved key residues of VP158, VP1147 and both VP272 / VP1147 as determined respectively by bnAb W153, W145 and W151-resistant mutants. Furthermore, the epitopes recognized by 20 strain-specific neutralization antibodies involved the key residues located on VP3 68 for A/AF72 (11/20) and VP3 175 position for A/GDMM/2013 (9/19), respectively, which revealed antigenic variation between different strains of serotype A. Analysis of antibody-driven variations on capsid of two virus strains showed a relatively stable VP2 and more variable VP3 and VP1. This study provided important information on conserve and variable antigen structures to design broad-spectrum molecular vaccine against FMDV serotype A.

PubMed: 37983290
DOI: 10.1371/journal.ppat.1011811

Experimental method

ELECTRON MICROSCOPY (3.75 Å)