Atomic structures of anthrax toxin protective antigen channels bound to partially unfolded lethal and edema factors

Nature Communications

Article

Bryan A. Krantz¹  Nathan J. Hardenbrook¹  Koyel Ghosal¹  Shiheng Liu²  Kang Zhou²  Z. Hong Zhou² 

[1] Department of Microbial Pathogenesis, University of Maryland, Baltimore, 21201, Baltimore, MD, USA;Department of Microbiology, Immunology and Molecular Genetics, University of California, 90095, Los Angeles, CA, USA;California NanoSystems Institute, University of California, 90095, Los Angeles, CA, USA;

关键词: ;   

DOI  :  10.1038/s41467-020-14658-6

 received in 2019-07-08, accepted in 2020-01-15,  发布年份 2020

来源: Springer

【 摘 要 】

Following assembly, the anthrax protective antigen (PA) forms an oligomeric translocon that unfolds and translocates either its lethal factor (LF) or edema factor (EF) into the host cell. Here, we report the cryo-EM structures of heptameric PA channels with partially unfolded LF and EF at 4.6 and 3.1-Å resolution, respectively. The first α helix and β strand of LF and EF unfold and dock into a deep amphipathic cleft, called the α clamp, which resides at the interface of two PA monomers. The α-clamp-helix interactions exhibit structural plasticity when comparing the structures of lethal and edema toxins. EF undergoes a largescale conformational rearrangement when forming the complex with the channel. A critical loop in the PA binding interface is displaced for about 4 Å, leading to the weakening of the binding interface prior to translocation. These structures provide key insights into the molecular mechanisms of translocation-coupled protein unfolding and translocation.

【 授权许可】

CC BY   
© The Author(s) 2020. corrected publication 2023

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Fig. 1