Journal article

An intermolecular electrostatic interaction controls the prepore-to-pore transition in a cholesterol-dependent cytolysin

Kristin R Wade, Eileen M Hotze, Michael J Kuiper, Craig J Morton, Michael W Parker, Rodney K Tweten

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | NATL ACAD SCIENCES | Published : 2015

Abstract

β-Barrel pore-forming toxins (βPFTs) form an obligatory oligomeric prepore intermediate before the formation of the β-barrel pore. The molecular components that control the critical prepore-to-pore transition remain unknown for βPFTs. Using the archetype βPFT perfringolysin O, we show that E183 of each monomer within the prepore complex forms an intermolecular electrostatic interaction with K336 of the adjacent monomer on completion of the prepore complex. The signal generated throughout the prepore complex by this interaction irrevocably commits it to the formation of the membrane-inserted giant β-barrel pore. This interaction supplies the free energy to overcome the energy barrier (determi..

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Grants

Awarded by NIH National Institute of Allergy and Infectious Diseases


Awarded by Victorian Life Sciences Computation Initiative Grant


Awarded by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES


Funding Acknowledgements

The technical assistance of P. Parrish and discussions with A. E. Johnson are appreciated. M.W.P. is a National Health and Medical Research Council of Australia Research Fellow. This work was supported by a grant from the NIH National Institute of Allergy and Infectious Diseases (1R01 AI037657), grants from the National Health and Medical Research Council of Australia, and a Victorian Life Sciences Computation Initiative Grant (VR0021) on its Peak Computing Facility at the University of Melbourne, an initiative of the Victorian Government. This work was partly carried out in the Australian Cancer Research Foundation Rational Drug Discovery Centre, with funding by the Victorian Government Operational Infrastructure Support Scheme to St Vincent's Institute.