Atomic Structures of Anthrax Prechannel Bound with Full-Length Lethal and Edema Factors.

Atomic Structures of Anthrax Prechannel Bound with Full-Length Lethal and Edema Factors.
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DOI:
10.1016/j.str.2020.05.009
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发表时间:
2020-08-04
期刊:
Structure (London, England : 1993)
影响因子:
--
通讯作者:
Zhou ZH
Zhou ZH
中科院分区:
其他
文献类型:
--
作者:
Zhou K;Liu S;Hardenbrook NJ;Cui Y;Krantz BA;Zhou ZH

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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)-这是单独招募的保护性抗原七聚体(PA 7)或八聚体(PA 8)prechannel和随后易位跨通道形成的内体膜上暴露于低pH值。在这里,我们报告的原子结构的PA 8 prechannel结合全长EF和LF。在这种易位前状态下,两种因子的N末端片段重新折叠成参与前通道α钳的α螺旋。募集到PA前通道暴露了两种毒素的最初埋藏的β链,并使EF的结构域组织成为可能。许多相互作用发生在PA前通道结合EF和LF的结构域界面上,导致毒素在易位前压实。我们的研究结果提供了关键的见解易位偶联蛋白的展开和易位的分子机制。
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 pre-translocation 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.
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