9BOF

16E10 Fab bound to norovirus GI.1 P domain

9BOF の概要

• エントリーDOI: 10.2210/pdb9bof/pdb
• EMDBエントリー: 44734
• 分子名称: Capsid protein VP1, 16E10 Light Chain, 16E10 Heavy Chain (3 entities in total)
• 機能のキーワード: norovirus, vp1, p-domain, antibody, viral protein, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Norovirus; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 159519.96

構造登録者

Olia, A.S.,Morano, N.C.,Shapiro, L.,Kwong, P.D. (登録日: 2024-05-03, 公開日: 2025-04-09, 最終更新日: 2025-10-22)

主引用文献

Rimkute, I.,Olia, A.S.,Suleiman, M.,Woods, K.D.,Bylund, T.,Morano, N.C.,Tully, E.S.,Verardi, R.,Bao, S.,Beddall, M.H.,Chaimongkol, N.,Donaldson, M.M.,Du, R.,Dulan, C.N.M.,Gorman, J.,Henry, A.R.,Schramm, C.A.,Sosnovtsev, S.V.,Stephens, T.,Todd, J.P.,Tsybovsky, Y.,Douek, D.C.,Green, K.Y.,Rawi, R.,Shapiro, L.,Zhou, T.,Kwong, P.D.,Roederer, M.
A broadly protective human antibody for GI genogroup noroviruses.
Nat Microbiol, 10:1227-1239, 2025

PubMed Abstract: Noroviruses infect millions each year, and while effective countermeasures are eagerly sought, none have been reported for the GI genogroup, first described more than 50 years ago. Here, to provide insight into GI norovirus neutralization, we isolated a broad GI antibody, 16E10, from a human blood donor and showed it neutralizes noroviruses in human enteroid cultures and abrogates or reduces infection in rhesus macaques. The cryogenic electron microscopy reconstruction of 16E10 with a norovirus protruding-domain dimer at 2.56-Å resolution reveals an exceptionally large binding surface, overlapping an antibody supersite, distal from host receptor-binding or cofactor-binding sites. Cryogenic electron microscopy reconstructions with virus-like particles (VLPs) showed that 16E10 disrupts protruding domains on the VLP surface and disassembles VLPs, altering viral organization required for avidity. While its epitope was generally conserved, 16E10 recognized multiple sequence-divergent residues, binding to which was enabled by corresponding cavities in the 16E10-norovirus interface. Broad recognition of noroviruses can thus incorporate sequence-divergent residues, through a cavity-based mechanism of diversity tolerance.

PubMed: 40211068
DOI: 10.1038/s41564-025-01952-6

実験手法

ELECTRON MICROSCOPY (2.61 Å)