Paper Citing NAMD - Abstract
Wade, Kristin R.; Hotze, Eileen M.; Kuiper, Michael J.; Morton, Craig J.; Parker, Michael W.; Tweten, Rodney K.
An intermolecular electrostatic interaction controls the prepore-to-pore transition in a cholesterol-dependent cytolysin
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 112:2204-2209, FEB 17 2015
beta-Barrel pore-forming toxins (beta PFTs) form an obligatory oligomeric prepore intermediate before the formation of the beta-barrel pore. The molecular components that control the critical prepore-to-pore transition remain unknown for beta PFTs. Using the archetype beta PFT 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 beta-barrel pore. This interaction supplies the free energy to overcome the energy barrier (determined here to be similar to 19 kcal/mol) to the prepore-to-pore transition by the coordinated disruption of a critical interface within each monomer. These studies provide the first insight to our knowledge into the molecular mechanism that controls the prepore-to-pore transition for a beta PFT.
