CPM Seminar

Criminal associations: How Bcl-2 family proteins conspire to make pores in membranes

Cécile Fradin

Department of Physics and Astronomy
McMaster University

The ordered creation of aqueous pores in phospholipid membranes by proteins requires a precisely orchestrated dance with participation of both proteins and lipids. The Bcl-2 family of proteins function in a concerted fashion to control mitochondrial outer membrane permeabilization, regarded as the point-of-no-return in apoptosis. To investigate this mechanism, we use biomimetic systems formed of model lipid membranes and purified Bcl-2 family proteins. We characterize these systems using single particle as well as ensemble biophysical techniques (fluorescence correlation techniques, single particle tracking, neutron and x-ray scattering). This has permitted the identification of several distinct conformational states as well as complex interaction patterns for these proteins as they progress from a fully soluble state to a fully membrane inserted and pore-forming state. Our work also outlines the importance of the lipids and the lipid membrane composition in this process. Understanding the complexity of the interaction network between the proteins in this family will eventually help with the development of better targeted anti-cancer drugs.