How many Bcl-2 family proteins does it take to form a pore in a lipid membrane?
Proteins from the Bcl-2 family preside over what is essentially the “point-of-no-return” in apoptosis. Pro-apoptotic members of the family promote outer mitochondrial membrane permeabilization and cell death, while anti-apoptotic members promote cell survival by blocking their pro-apoptotic counterparts. The complexity of the process is compounded due to the different conformations each of the proteins can adopt, as well as by the important role played by the lipids in mediating protein-protein interactions. We use reconstituted membrane systems, and both fluorescence and scattering methods, to quantitatively characterize the pathway leading to membrane permeabilization by pro-apoptotic proteins Bax and Bid. Our measurements show that lipid composition affects specific steps in the pathway. Charged lipids influence the initial recruitment of Bid to the membrane, cardiolipin facilitates protein activation by triggering a conformational change in Bid, and cholesterol blocks Bax insertion into the membrane.
Université McMaster dHamilton, Canada
Domain 2 - UMR 3664 - Nuclear Dynamics