Atomic Structures of Anthrax Prechannel Bound with Full-Length Lethal and Edema Factors
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AbstractPathogenesis 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.
SponsorsThis work was supported in part by grants from the National Science Foundation (NSF, under grant no. DMR-1548924 ) and by grants from the National Institutes of Health ( R01GM071940/AI094386/DE025567 to Z.H.Z. and R21AI124020 to B.A.K.) and the Training Program in Integrative Membrane Biology at the University of Maryland , Baltimore ( T32GM008181 ).
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85086940547&doi=10.1016%2fj.str.2020.05.009&partnerID=40&md5=2e660e4d918b128178002b48fae2ca43; http://hdl.handle.net/10713/13241
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