Crystallography and ISMB Birkbeck College London |
The pore-forming toxin pneumolysin is a member of a large family of highly conserved, cholesterol binding toxins. These toxins are released from gram positive bacteria as soluble monomeric proteins, which then assemble into prepore oligomers on the surface of cholesterol-containing cell membranes. The prepores then puncture the membrane to form very large pores containing 30-50 subunits, with a channel diameter around 250 Angstroms. The structures of the soluble form of two members of the family, perfringolysin and intermedilysin, have been determined by X-ray crystallography (Rossjohn et al, 1997, Cell 89, 685-692; 1PFO; Polekhina et al, 2005, PNAS 102, 600-605; 1S3R). We have been studying oligomeric forms of pneumolysin bound to liposomes by cryo EM, image processing and atomic structure docking using the domains of perfringolysin. In the 3D surface views (top), the protein rings are shown in purple and the surrounding liposome membrane in blue. The sections through the maps show the fitted domain structures. The work has been funded by the BBSRC.
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Host-pathogen interactions | |
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