Atomic structure of anthrax PA pore elucidates toxin translocation

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Atomic structure of anthrax PA pore elucidates toxin translocation

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Title: Atomic structure of anthrax PA pore elucidates toxin translocation
Author: Jiang, Jiansen; Pentelute, Bradley L.; Collier, R. John; Zhou, Z. Hong

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Citation: Jiang, Jiansen, Bradley L. Pentelute, R. John Collier, and Z. Hong Zhou. 2015. “Atomic structure of anthrax PA pore elucidates toxin translocation.” Nature 521 (7553): 545-549. doi:10.1038/nature14247. http://dx.doi.org/10.1038/nature14247.
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Abstract: Summary Anthrax toxin, comprising protective antigen (PA), lethal factor (LF) and edema factor (EF), is the major virulence factor of Bacillus anthracis, an agent that causes high mortality in human and animals. PA forms oligomeric prepores that undergo conversion to membrane-spanning pores by endosomal acidification, and these pores translocate the enzymes LF and EF into the cytosol of target cells1. PA is not only a vaccine component and therapeutic target for anthrax infections but also an excellent model system for understanding the mechanism of protein translocation. Based on biochemical and electrophysiological results, researchers have proposed that a Φ-clamp composed of Phe427 residues of PA catalyzes protein translocation via a charge-state dependent Brownian ratchet2–9. Although atomic structures of PA prepores are available10–14, how PA senses low pH, converts to active pore and translocates LF and EF are not well defined without an atomic model of the PA pore. Here, by cryo electron microscopy (cryoEM) with direct electron counting, we have determined the PA pore structure at 2.9-Å resolution. The structure reveals the long-sought-after catalytic Φ-clamp and the membrane-spanning translocation channel, and supports the Brownian ratchet model for protein translocation. Comparisons of four structures reveal conformational changes in prepore to pore conversion that support a multi-step mechanism by which low-pH is sensed and the membrane-spanning channel is formed.
Published Version: doi:10.1038/nature14247
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4519040/pdf/
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Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:23845219
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