7FEI

Complex of FMDV A/WH/CHA/09 and bovine neutralizing scFv antibody R55

7FEI の概要

• エントリーDOI: 10.2210/pdb7fei/pdb
• EMDBエントリー: 31555
• 分子名称: Capsid protein VP0, IG HEAVY CHAIN VARIABLE REGION, IG LAMDA CHAIN VARIABLE REGION, ... (6 entities in total)
• 機能のキーワード: virus
• 由来する生物種: Bos taurus; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 107381.42

構造登録者

He, Y.,Li, K.,Lou, Z. (登録日: 2021-07-20, 公開日: 2021-09-29, 最終更新日: 2024-10-23)

主引用文献

He, Y.,Li, K.,Wang, L.,Sun, Z.,Cao, Y.,Li, P.,Sun, P.,Bao, H.,Zhou, S.,Wang, S.,Bai, X.,Liu, X.,Zhao, L.,Fan, X.,Liu, Z.,Lu, Z.,Yang, C.,Lou, Z.
Structures of Foot-and-Mouth Disease Virus with Bovine Neutralizing Antibodies Reveal the Determinant of Intraserotype Cross-Neutralization.
J.Virol., 95:e0130821-e0130821, 2021

PubMed Abstract: Foot-and-mouth disease virus (FMDV) exhibits broad antigenic diversity with poor intraserotype cross-neutralizing activity. Studies of the determinant involved in this diversity are essential for the development of broadly protective vaccines. In this work, we isolated a bovine antibody, designated R55, that displays cross-reaction with both FMDV A/AF/72 (hereafter named FMDV-AAF) and FMDV A/WH/09 (hereafter named FMDV-AWH) but only has a neutralizing effect on FMDV-AWH. Near-atomic resolution structures of FMDV-AAF-R55 and FMDV-AWH-R55 show that R55 engages the capsids of both FMDV-AAF and FMDV-AWH near the icosahedral 3-fold axis and binds to the βB and BC/HI-loops of VP2 and to the B-B knob of VP3. The common interaction residues are highly conserved, which is the major determinant for cross-reaction with both FMDV-AAF and FMDV-AWH. In addition, the cryo-EM structure of the FMDV-AWH-R55 complex also shows that R55 binds to E70 located at the VP3 BC-loop in an adjacent pentamer, which enhances the acid and thermal stabilities of the viral capsid. This may prevent capsid dissociation and genome release into host cells, eventually leading to neutralization of the viral infection. In contrast, R55 binds only to the FMDV-AAF capsid within one pentamer due to the E70G variation, which neither enhances capsid stability nor neutralizes FMDV-AAF infection. The E70G mutation is the major determinant involved in the neutralizing differences between FMDV-AWH and FMDV-AAF. The crucial amino acid E70 is a key component of the neutralizing epitopes, which may aid in the development of broadly protective vaccines. Foot-and-mouth disease virus (FMDV) causes a highly contagious and economically devastating disease in cloven-hoofed animals, and neutralizing antibodies play critical roles in the defense against viral infections. Here, we isolated a bovine antibody (R55) using the single B cell antibody isolation technique. Enzyme-linked immunosorbent assays (ELISA) and virus neutralization tests (VNT) showed that R55 displays cross-reactions with both FMDV-AWH and FMDV-AAF but only has a neutralizing effect on FMDV-AWH. Cryo-EM structures, fluorescence-based thermal stability assays and acid stability assays showed that R55 engages the capsid of FMDV-AWH near the icosahedral 3-fold axis and informs an interpentamer epitope, which overstabilizes virions to hinder capsid dissociation to release the genome, eventually leading to neutralization of viral infection. The crucial amino acid E70 forms a key component of neutralizing epitopes, and the determination of the E70G mutation involved in the neutralizing differences between FMDV-AWH and FMDV-AAF could aid in the development of broadly protective vaccines.

PubMed: 34586859
DOI: 10.1128/JVI.01308-21

実験手法

ELECTRON MICROSCOPY (3.91 Å)