Structural investigations of pneumolysin/lipid complexes

Pneumolysin, a virulence factor from the human pathogen Streptococcus pneum oniae, is a water-soluble protein which forms ring-shaped oligomeric struct ures upon binding to cholesterol-containing lipid membranes. It induces ves icle aggregation, membrane pore formation and withdrawal of lipid material into non-bilayer proteolipid complexes. Solid-state magic angle spinning an d wideline static NMR, together with freeze-fracture electron microscopy, a re used to characterize the phase changes in fully hydrated cholesterol-con taining lipid membranes induced by the addition of pneumolysin. A structura l model for the proteolipid complexes is proposed where a 30-50-meric pneum olysin ring lines the inside of a lipid torus. Cholesterol is found to be e ssential to the fusogenic action of pneumolysin.