8E8X

9H2 Fab-Sabin poliovirus 3 complex

8E8X の概要

• エントリーDOI: 10.2210/pdb8e8x/pdb
• EMDBエントリー: 27943 27947 27948 27949 27950 27951
• 分子名称: Capsid protein VP1, Capsid protein VP2, Capsid protein VP3, ... (7 entities in total)
• 機能のキーワード: complex, fab, poliovirus, neutralizing, virus-immune system complex, virus/immune system
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 120090.02

構造登録者

Charnesky, A.J. (登録日: 2022-08-26, 公開日: 2023-06-21, 最終更新日: 2025-06-04)

主引用文献

Charnesky, A.J.,Faust, J.E.,Lee, H.,Puligedda, R.D.,Goetschius, D.J.,DiNunno, N.M.,Thapa, V.,Bator, C.M.,Cho, S.H.J.,Wahid, R.,Mahmood, K.,Dessain, S.,Chumakov, K.M.,Rosenfeld, A.,Hafenstein, S.L.
A human monoclonal antibody binds within the poliovirus receptor-binding site to neutralize all three serotypes.
Nat Commun, 14:6335-6335, 2023

PubMed Abstract: Global eradication of poliovirus remains elusive, and it is critical to develop next generation vaccines and antivirals. In support of this goal, we map the epitope of human monoclonal antibody 9H2 which is able to neutralize the three serotypes of poliovirus. Using cryo-EM we solve the near-atomic structures of 9H2 fragments (Fab) bound to capsids of poliovirus serotypes 1, 2, and 3. The Fab-virus complexes show that Fab interacts with the same binding mode for each serotype and at the same angle of interaction relative to the capsid surface. For each of the Fab-virus complexes, we find that the binding site overlaps with the poliovirus receptor (PVR) binding site and maps across and into a depression in the capsid called the canyon. No conformational changes to the capsid are induced by Fab binding for any complex. Competition binding experiments between 9H2 and PVR reveal that 9H2 impedes receptor binding. Thus, 9H2 outcompetes the receptor to neutralize poliovirus. The ability to neutralize all three serotypes, coupled with the critical importance of the conserved receptor binding site make 9H2 an attractive antiviral candidate for future development.

PubMed: 37816742
DOI: 10.1038/s41467-023-41052-9

実験手法

ELECTRON MICROSCOPY (2.91 Å)