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

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 (determined here to be ∼ 19 kcal/mol) to the prepore-to-pore transition by the coordinated disruption of a c

SUBMITTER: Wade KR 

PROVIDER: S-EPMC4343107 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature