Allosteric Regulation of BH3 Proteins in Bcl-xL Complexes Enables Switch-like Activation of Bax (Molecular Cell)

The affinities of full-length Bcl-2 family proteins measured in assays containing mitochondria reveal that at physiological concentrations, the pro-apoptotic BH3 protein Bad does not displace sufficient activator BH3 proteins from anti-apoptotic Bcl-xL to activate the pro-apoptotic protein Bax and elicit apoptosis. Instead, Bad mediates allosteric activation of activator BH3 proteins that remain bound to Bcl-xL complexes, explaining how sensitizer BH3 proteins such as Bad promote switch-like activation of pro-apoptotic Bax and induce apoptosis under physiological conditions.