Open AccessThe domains of a cholesterol-dependent cytolysin undergo a major FRET-detected rearrangement during pore formation
Author(s) -
Rajesh Ramachandran,
Rodney K. Tweten,
Arthur E. Johnson
Publication year - 2005
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0500556102
Subject(s) - oligomer , membrane , monomer , bilayer , förster resonance energy transfer , lipid bilayer , crystallography , biophysics , chemistry , transmembrane protein , cytolysin , biology , biochemistry , polymer chemistry , polymer , receptor , organic chemistry , quantum mechanics , fluorescence , virulence , gene , physics
FRET measurements were used to determine the domain-specific topography of perfringolysin O, a pore-forming toxin, on a membrane surface at different stages of pore formation. The data reveal that the elongated toxin monomer binds stably to the membrane in an "end-on" orientation, with its long axis approximately perpendicular to the plane of the membrane bilayer. This orientation is largely retained even after monomer association to form an oligomeric prepore complex. The domain 3 (D3) polypeptide segments that ultimately form transmembrane beta-hairpins remain far above the membrane surface in both the membrane-bound monomer and prepore oligomer. Upon pore formation, these segments enter the bilayer, whereas D1 moves to a position that is substantially closer to the membrane. Therefore, the extended D2 beta-structure that connects D1 to membrane-bound D4 appears to bend or otherwise reconfigure during the prepore-to-pore transition of the perfringolysin O oligomer.