Structural biology of proteins involved in infection

Summary The b-barrel pore-forming toxins constitute the largest group of functionally related toxins/proteins and are expressed in many species in the prokaryotic and eukaryotic kingdoms and also include the membrane attack complex/perforin (MACPF) family of mammalian immune defence proteins. Despite their widespread occurrence and role in bacterial pathogenesis and immune defence, the detailed mechanism by which they form pores remains an enigma. The overall aim here is to visualise the 3D structures of family members as a basis for functional studies to reveal the molecular details of how these toxins insert into membranes to form b-barrel pores and how the process is regulated.

Project Details

The b-barrel pore-forming toxins constitute the largest group of functionally related toxins/proteins and are expressed in many species in the prokaryotic and eukaryotic kingdoms and also include the membrane attack complex/perforin (MACPF) family of mammalian immune defence proteins. Despite their widespread occurrence and role in bacterial pathogenesis and immune defence, the detailed mechanism by which they form pores remains an enigma. The overall aim here is to visualise the 3D structures of family members as a basis for functional studies to reveal the molecular details of how these toxins insert into membranes to form b-barrel pores and how the process is regulated. The structures will shed light on one of the most fundamental biological events (namely, protein insertion into cell membranes) and also provide the basis for the design of novel tools with various biotechnology applications and the design of novel antibiotics.

This project is conducted in St Vincent’s Institute of Medical Research, Structural Biology Unit.