7KXR

Protective antigen pore translocating lethal factor N-terminal domain

Summary for 7KXR

• Entry DOI: 10.2210/pdb7kxr/pdb
• EMDB information: 23066
• Descriptor: Lethal factor, Protective antigen, CALCIUM ION (3 entities in total)
• Functional Keywords: translocation, complex, anthrax, refolding, toxin
• Biological source: Bacillus anthracis; More
• Total number of polymer chains: 8
• Total formula weight: 472214.58

Authors

Machen, A.J.,Freudenthal, B.D. (deposition date: 2020-12-04, release date: 2021-07-14, Last modification date: 2024-03-06)

Primary citation

Machen, A.J.,Fisher, M.T.,Freudenthal, B.D.
Anthrax toxin translocation complex reveals insight into the lethal factor unfolding and refolding mechanism.
Sci Rep, 11:13038-13038, 2021

PubMed Abstract: 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.

PubMed: 34158520
DOI: 10.1038/s41598-021-91596-3

Experimental method

ELECTRON MICROSCOPY (3.3 Å)