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TitleAnthrax toxin translocation complex reveals insight into the lethal factor unfolding and refolding mechanism.
Journal, issue, pagesSci Rep, Vol. 11, Issue 1, Page 13038, Year 2021
Publish dateJun 22, 2021
AuthorsAlexandra J Machen / Mark T Fisher / Bret D Freudenthal /
PubMed AbstractTranslocation is essential to the anthrax toxin mechanism. Protective antigen (PA), the binding component of this AB toxin, forms an oligomeric pore that translocates lethal factor (LF) or edema ...Translocation is essential to the anthrax toxin mechanism. Protective antigen (PA), the binding component of this AB toxin, forms an oligomeric pore that translocates lethal factor (LF) or edema factor, the active components of the toxin, into the cell. Structural details of the translocation process have remained elusive despite their biological importance. To overcome the technical challenges of studying translocation intermediates, we developed a method to immobilize, transition, and stabilize anthrax toxin to mimic important physiological steps in the intoxication process. Here, we report a cryoEM snapshot of PA translocating the N-terminal domain of LF (LF). The resulting 3.3 Å structure of the complex shows density of partially unfolded LF near the canonical PA binding site. Interestingly, we also observe density consistent with an α helix emerging from the 100 Å β barrel channel suggesting LF secondary structural elements begin to refold in the pore channel. We conclude the anthrax toxin β barrel aids in efficient folding of its enzymatic payload prior to channel exit. Our hypothesized refolding mechanism has broader implications for pore length of other protein translocating toxins.
External linksSci Rep / PubMed:34158520 / PubMed Central
MethodsEM (single particle)
Resolution3.3 Å
Structure data

23066

7kxr

EMDB-23066, PDB-7kxr:
Protective antigen pore translocating lethal factor N-terminal domain
Method: EM (single particle) / Resolution: 3.3 Å

Chemicals

ChemComp-CA:
Unknown entry

Source
  • bacillus anthracis (anthrax bacterium)
KeywordsTOXIN / translocation / complex / anthrax / refolding

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