Journal article

An Intermolecular pi-Stacking Interaction Drives Conformational Changes Necessary to beta-Barrel Formation in a Pore-Forming Toxin

Joshua R Burns, Craig J Morton, Michael W Parker, Rodney K Tweten

mBio | AMER SOC MICROBIOLOGY | Published : 2019


The crystal structures of the soluble monomers of the pore-forming cholesterol-dependent cytolysins (CDCs) contain two α-helical bundles that flank a twisted core β-sheet. This protein fold is the hallmark of the CDCs, as well as of the membrane attack complex/perforin immune defense proteins and the stonefish toxins. To form the β-barrel pore, a core β-sheet is flattened to align the membrane-spanning β-hairpins. Concomitantly with this conformational change, the two α-helical bundles that flank the core β-sheet break their restraining contacts and refold into two membrane-spanning β-hairpins of the β-barrel pore. The studies herein show that in the monomer structure of the archetype CDC pe..

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Awarded by NIH NIAID

Awarded by Australian Research Council

Awarded by National Health and Medical Research Council of Australia


Funding Acknowledgements

This work was supported by a grant from the NIH NIAID (1R37 AI037657) to R.K.T. and by an Australian Research Council discovery grant (DP160101874) and a National Health and Medical Research Council of Australia fellowship (APP1117183) to M.W.P. Funding from the Victorian Government Operational Infrastructure Support Scheme to St. Vincent's Institute is acknowledged.