Structure of Bcl-xL-Bak peptide complex : recognition between regulators of Apoptosis.

Abstract

Heterodimerization between members of the Bcl-2 family of proteins is a key event in the

regulation of programmed cell death. The molecular basis for heterodimer formation was

investigated by determination of the solution structure of a complex between the survival

protein Bcl-xL and the death-promoting region of the Bcl-2–related protein Bak. The

structure and binding affinities of mutant Bak peptides indicate that the Bak peptide

adopts an amphipathic α helix that interacts with Bcl-xL through hydrophobic and

electrostatic interactions. Mutations in full-length Bak that disrupt either type of interaction

inhibit the ability of Bak to heterodimerize with Bcl-xL.