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Atomic Structures of Anthrax Prechannel Bound with Full-Length Lethal and Edema Factors.
Structure ( IF 5.7 ) Pub Date : 2020-06-09 , DOI: 10.1016/j.str.2020.05.009
Kang Zhou 1 , Shiheng Liu 2 , Nathan J Hardenbrook 3 , Yanxiang Cui 1 , Bryan A Krantz 3 , Z Hong Zhou 2
Affiliation  

Pathogenesis of anthrax disease involves two cytotoxic enzymes—edema factor (EF) and lethal factor (LF)—which are individually recruited by the protective antigen heptamer (PA7) or octamer (PA8) prechannel and subsequently translocated across channels formed on the endosomal membrane upon exposure to low pH. Here, we report the atomic structures of PA8 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.



中文翻译:

与全长致死和水肿因子结合的炭疽前通道的原子结构。

炭疽病的发病机制涉及两种细胞毒性酶——水肿因子 (EF) 和致死因子 (LF)——它们分别被保护性抗原七聚体 (PA 7 ) 或八聚体 (PA 8 ) 前通道募集,随后跨内体上形成的通道易位膜暴露于低 pH 值时。在这里,我们报告了 PA 8的原子结构prechannel-bound 全长 EF 和 LF。在这种预易位状态下,两个因子的 N 端片段重新折叠成一个 α 螺旋,与前通道的 α 夹钳接合。对 PA 前通道的招募暴露了最初隐藏的两种毒素的 β 链,并使 EF 的域组织成为可能。许多相互作用发生在 PA 通道前结合 EF 和 LF 的域界面上,导致易位之前的毒素压实。我们的研究结果为易位偶联蛋白展开和易位的分子机制提供了关键见解。

更新日期:2020-08-04
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