7T4E

Prepore structure of pore-forming toxin Epx1

7T4E の概要

• エントリーDOI: 10.2210/pdb7t4e/pdb
• EMDBエントリー: 25673
• 分子名称: Epx1 (1 entity in total)
• 機能のキーワード: pore-forming toxin, toxin
• 由来する生物種: Enterococcus faecalis
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 296138.16

構造登録者

Xiong, X.Z.,Yang, P.,Dong, M.,Abraham, J. (登録日: 2021-12-09, 公開日: 2022-03-16, 最終更新日: 2024-02-28)

主引用文献

Xiong, X.,Tian, S.,Yang, P.,Lebreton, F.,Bao, H.,Sheng, K.,Yin, L.,Chen, P.,Zhang, J.,Qi, W.,Ruan, J.,Wu, H.,Chen, H.,Breault, D.T.,Wu, H.,Earl, A.M.,Gilmore, M.S.,Abraham, J.,Dong, M.
Emerging enterococcus pore-forming toxins with MHC/HLA-I as receptors.
Cell, 185:1157-, 2022

PubMed Abstract: Enterococci are a part of human microbiota and a leading cause of multidrug resistant infections. Here, we identify a family of Enterococcus pore-forming toxins (Epxs) in E. faecalis, E. faecium, and E. hirae strains isolated across the globe. Structural studies reveal that Epxs form a branch of β-barrel pore-forming toxins with a β-barrel protrusion (designated the top domain) sitting atop the cap domain. Through a genome-wide CRISPR-Cas9 screen, we identify human leukocyte antigen class I (HLA-I) complex as a receptor for two members (Epx2 and Epx3), which preferentially recognize human HLA-I and homologous MHC-I of equine, bovine, and porcine, but not murine, origin. Interferon exposure, which stimulates MHC-I expression, sensitizes human cells and intestinal organoids to Epx2 and Epx3 toxicity. Co-culture with Epx2-harboring E. faecium damages human peripheral blood mononuclear cells and intestinal organoids, and this toxicity is neutralized by an Epx2 antibody, demonstrating the toxin-mediated virulence of Epx-carrying Enterococcus.

PubMed: 35259335
DOI: 10.1016/j.cell.2022.02.002

実験手法

ELECTRON MICROSCOPY (2.87 Å)