8JG5

Cryo-EM structure of the GI.4 Chiba VLP complexed with the CV-1A1 Fv-clasp

8JG5 の概要

• エントリーDOI: 10.2210/pdb8jg5/pdb
• EMDBエントリー: 36223
• 分子名称: VP1, VH,SARAH, VL,SARAH (3 entities in total)
• 機能のキーワード: norovirus, gi.4, virus like particle, human monoclonal antibody, fv-clasp, virus
• 由来する生物種: Chiba virus; 詳細
• タンパク質・核酸の鎖数: 7
• 化学式量合計: 250405.80

構造登録者

Hosaka, T.,Katsura, K.,Kimura-Someya, T.,Someya, Y.,Shirouzu, M. (登録日: 2023-05-19, 公開日: 2024-04-17, 最終更新日: 2025-06-18)

主引用文献

Kimura-Someya, T.,Katsura, K.,Kato-Murayama, M.,Hosaka, T.,Uchikubo-Kamo, T.,Ihara, K.,Hanada, K.,Sato, S.,Murayama, K.,Kataoka, M.,Shirouzu, M.,Someya, Y.
Structural analyses of the GI.4 norovirus by cryo-electron microscopy and X-ray crystallography revealing binding sites for human monoclonal antibodies.
J.Virol., 98:e0019724-e0019724, 2024

PubMed Abstract: Noroviruses are major causative agents of acute nonbacterial gastroenteritis in humans. There are neither antiviral therapeutic agents nor vaccines for noroviruses at this time. To evaluate the potential usefulness of two previously isolated human monoclonal antibody fragments, CV-1A1 and CV-2F5, we first conducted a single-particle analysis to determine the cryo-electron microscopy structure of virus-like particles (VLPs) from the genogroup I genotype 4 (GI.4) Chiba strain uniformly coated with CV-1A1 fragments. The results revealed that the GI.4-specific CV-1A1 antibody bound to the P2 subdomain, in which amino acids are less conserved and variable. Interestingly, a part of the CV-1A1 intrudes into the histo-blood group antigen-binding site, suggesting that this antibody might exert neutralizing activity. Next, we determined the crystal structure of the protruding (P) domain of the capsid protein in the complex form with the CV-2F5 antibody fragment. Consistent with the cross-reactivity, the CV-2F5 bound to the P1 subdomain, which is rich in amino acids conserved among the GI strains, and moreover induced a disruption of Chiba VLPs. These results suggest that the broadly reactive CV-2F5 antibody can be used as both a universal detection reagent and an antiviral drug for GI noroviruses.

PubMed: 38593321
DOI: 10.1128/jvi.00197-24

実験手法

ELECTRON MICROSCOPY (3.04 Å)