National Institutes of Health/National Library of Medicine (NIH/NLM)
R01GM071940/AI094386/DE025567
米国
National Institutes of Health/National Library of Medicine (NIH/NLM)
R21AI124020
米国
引用
ジャーナル: Structure / 年: 2020 タイトル: Atomic Structures of Anthrax Prechannel Bound with Full-Length Lethal and Edema Factors. 著者: Kang Zhou / Shiheng Liu / Nathan J Hardenbrook / Yanxiang Cui / Bryan A Krantz / Z Hong Zhou / 要旨: Pathogenesis of anthrax disease involves two cytotoxic enzymes-edema factor (EF) and lethal factor (LF)-which are individually recruited by the protective antigen heptamer (PA) or octamer (PA) ...Pathogenesis of anthrax disease involves two cytotoxic enzymes-edema factor (EF) and lethal factor (LF)-which are individually recruited by the protective antigen heptamer (PA) or octamer (PA) prechannel and subsequently translocated across channels formed on the endosomal membrane upon exposure to low pH. Here, we report the atomic structures of PA prechannel-bound full-length EF and LF. In this pretranslocation state, the N-terminal segment of both factors refolds into an α helix engaged in the α clamp of the prechannel. Recruitment to the PA prechannel exposes an originally buried β strand of both toxins and enables domain organization of EF. Many interactions occur on domain interfaces in both PA prechannel-bound EF and LF, leading to toxin compaction prior to translocation. Our results provide key insights into the molecular mechanisms of translocation-coupled protein unfolding and translocation.