Structure of Bcl-x L -Bak Peptide Complex: Recognition Between Regulators of Apoptosis

• DOI: 10.1126/science.275.5302.983
• Publication Date: 2002-07-27T09:37:56Z
• Authors: Michael Sattler; Heng Liang; David Nettesheim; Robert P. Meadows; John E. Harlan; Matthias Eberstadt; Ho Sup Yoon; Suzanne B. Shuker; Brian S. Chang; Andy J. Minn; Craig B. Thompson; Stephen W. Fesik
• Keywords: Models, Molecular; 0301 basic medicine; Magnetic Resonance Spectroscopy; Protein Conformation; Molecular Sequence Data; bcl-X Protein; Membrane Proteins; Apoptosis; Crystallography, X-Ray; Protein Structure, Secondary; 03 medical and health sciences; bcl-2 Homologous Antagonist-Killer Protein; Proto-Oncogene Proteins c-bcl-2; :Business::Public relations::Crisis communication [DRNTU]; Proto-Oncogene Proteins; Amino Acid Sequence; Dimerization; Sequence Deletion

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-x L 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-x L 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-x L .