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

Abstract

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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Grants

Awarded by NIH NIAID


Awarded by Australian Research Council


Awarded by National Health and Medical Research Council of Australia


Awarded by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES


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.