A New Model for Pore Formation by Cholesterol-Dependent Cytolysins (original) (raw)
Figure 1
CDC domain organisation and mechanism of pore formation.
A. Crystal structure of the archetypal CDC PFO and its schematic representation. Domain 1 is coloured blue, Domain 2 coloured green, Domain 3 coloured red, orange and pink and Domain 4 coloured yellow. Together Domains 1 and 3 form the ‘head’ domain distantly related to the MACPF domain. Specific transmembrane regions include the TransMembrane Helices (TMH) 1 coloured orange and TMH2 coloured pink; the strand β5 and the undecapeptide loop are indicated. B. Current model of CDC pore formation. After the membrane binding event, monomers oligomerize into a ring-like structure (30 to 50 monomers; prepore). Upon formation of the oligomeric pore, both helical clusters insert into the transmembrane bilayer (grey bars) as two β-hairpins (orange and pink) part of a giant β-sheet barrel. Concomitantly Domain 1 is subject to a vertical collapse associated with a proposed “buckling” of Domain 2 (reviewed in [1], [58]).