9HV2

Crystal structure of tri-specific FMDV mAb-34 Fab

9HV2 の概要

• エントリーDOI: 10.2210/pdb9hv2/pdb
• 関連するPDBエントリー: 9HV1
• 分子名称: heavy chain, light chain (3 entities in total)
• 機能のキーワード: foot-and-mouth disease virus, cattle antibody, cross-reactive, linear epitope, antibody structure, immune system
• 由来する生物種: Bos taurus; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 95565.81

構造登録者

Ren, J.,Duyvesteyn, H.M.E.,Stuart, D.I. (登録日: 2024-12-24, 公開日: 2026-01-14, 最終更新日: 2026-04-15)

主引用文献

Bonnet-Di Placido, M.,Duyvesteyn, H.M.E.,Steyn, A.W.,Hay, A.L.,Porta, C.,Valdez, K.R.,Lokhman, E.,Crossley, S.,Hanson, K.,Mwangi, W.N.,Munir, D.,Perez-Martin, E.,Knowles, N.J.,Burman, A.,Yassin, A.A.,Asfor, A.,Faralla, C.,Lam, K.J.,McComb, R.,Leifeld, C.,Pietersz, K.,King, D.P.,van den Born, E.,Duncan, S.K.,Charleston, B.,Fry, E.E.,Ren, J.,Stuart, D.I.,Hammond, J.A.
Cattle antibodies identify a cross-serotype broadly neutralising foot-and-mouth disease virus epitope.
Npj Vaccines, 2026

PubMed Abstract: Foot-and-mouth disease virus (FMDV) causes a devastating disease that threatens global food security. Vaccination is hindered by antigenic diversity across serotypes. To identify cross-serotype neutralising epitopes, we isolated 24 FMDV-specific antibodies from cattle sequentially vaccinated with antigens from four serotypes, of which three neutralised three vaccine strains. These three antibodies neutralised 21 and bound 59 additional topotypes across O, A, Asia 1, and C serotypes. Cryo-EM complexes of Fabs with FMD virus-like particles indicated all three recognise a common flexible epitope at the VP1 C-terminus, confirmed by binding competition. Crystallography and structural modelling revealed that a normally inaccessible surface of the hydrophobic VP1 C-terminal peptides inserts into a similar groove in all three antibodies. Comparison of neutralisation activity and integrin receptor blocking by whole antibodies, F(ab')s, and Fabs suggests neutralisation is mediated by Fc steric hindrance of receptor binding. This cryptic, linear, and cross-serotype neutralising epitope may inform improved FMD vaccines.

PubMed: 41927576
DOI: 10.1038/s41541-026-01427-7

実験手法

X-RAY DIFFRACTION (1.77 Å)