9RIP

EV-A71 (genotype B5) in complex with 17-2-12A Fab

9RIP の概要

• エントリーDOI: 10.2210/pdb9rip/pdb
• 関連するPDBエントリー: 9RIN 9RIO
• EMDBエントリー: 54003
• 分子名称: Genome polyprotein, Capsid protein, light chain, ... (7 entities in total)
• 機能のキーワード: hand-foot-and-mouth disease, hfmd, enterovirus 71 (ev-a71), human antibody, virus, 17-2-12a
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 143294.92

構造登録者

Zhou, D.,Ren, J.,Stuart, D.I. (登録日: 2025-06-11, 公開日: 2026-04-29, 最終更新日: 2026-06-17)

主引用文献

Zhou, D.,Kotecha, A.,Kelly, J.T.,Huang, P.N.,Chen, Y.Y.,Walter, T.S.,Duyvesteyn, H.M.E.,Owens, R.J.,Ho, S.Y.,Lin, T.Y.,Fry, E.E.,Ren, J.,Huang, K.A.,Stuart, D.I.
Structural and functional mapping of protective human monoclonal antibodies against enterovirus A71.
Sci Adv, 12:eaee8217-eaee8217, 2026

PubMed Abstract: EV-A71 has been responsible for recent severe HFMD outbreaks. We report structures for 12 potently neutralizing human anti-EV-A71 monoclonal antibody Fabs, alone and complexed with virus. Most recognize the native antigenic state with epitopes that span interfaces, together covering 85% of the capsid surface. The majority (8 of 12) bind the canyon, while the others cluster around the icosahedral two- and threefold axes. Blocking SCARB2 receptor binding likely contributes to neutralization for all, and a subset induces empty particles. A predominant gene family (IGHV4-39) does not dictate a common binding pose. Long CDR-H3 loops are frequently key to binding, especially at the canyon, suggesting that antigenicity data based on antibodies with shorter CDR3s (e.g., murine) may be misleading. This dataset reveals neutralization mechanisms for recently circulating EV-A71 genotypes, which will inform immunotherapies. We demonstrate synergy in vitro between canyon binding and both two- and threefold binding antibodies to increase neutralization potency.

PubMed: 42247493
DOI: 10.1126/sciadv.aee8217

実験手法

ELECTRON MICROSCOPY (3.1 Å)