6UJI

Low resolution crystal structure (5.5 A) of the anthrax toxin protective antigen heptamer prepore D425A mutant

6UJI の概要

• エントリーDOI: 10.2210/pdb6uji/pdb
• 分子名称: Protective antigen PA-63 (1 entity in total)
• 機能のキーワード: anthrax toxin, pa63 heptamer, toxin
• 由来する生物種: Bacillus anthracis
• タンパク質・核酸の鎖数: 14
• 化学式量合計: 888657.00

構造登録者

Lovell, S.,Mehzabeen, N.,Battaile, K.P.,Bann, J.G. (登録日: 2019-10-03, 公開日: 2020-10-07, 最終更新日: 2023-10-11)

主引用文献

Scott, H.,Huang, W.,Andra, K.,Mamillapalli, S.,Gonti, S.,Day, A.,Zhang, K.,Mehzabeen, N.,Battaile, K.P.,Raju, A.,Lovell, S.,Bann, J.G.,Taylor, D.J.
Structure of the anthrax protective antigen D425A dominant negative mutant reveals a stalled intermediate state of pore maturation.
J.Mol.Biol., :167548-167548, 2022

PubMed Abstract: The tripartite protein complex produced by anthrax bacteria (Bacillus anthracis) is a member of the AB family of β-barrel pore-forming toxins. The protective antigen (PA) component forms an oligomeric prepore that assembles on the host cell surface and serves as a scaffold for binding of lethal and edema factors. Following endocytosis, the acidic environment of the late endosome triggers a pH-induced conformational rearrangement to promote maturation of the PA prepore to a functional, membrane spanning pore that facilitates delivery of lethal and edema factors to the cytosol of the infected host. Here, we show that the dominant-negative D425A mutant of PA stalls anthrax pore maturation in an intermediate state at acidic pH. Our 2.7 Å cryo-EM structure of the intermediate state reveals structural rearrangements that involve constriction of the oligomeric pore combined with an intramolecular dissociation of the pore-forming module. In addition to defining the early stages of anthrax pore maturation, the structure identifies asymmetric conformational changes in the oligomeric pore that are influenced by the precise configuration of adjacent protomers.

PubMed: 35304125
DOI: 10.1016/j.jmb.2022.167548

実験手法

X-RAY DIFFRACTION (5.5 Å)