title: 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 alpha 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.
authors.affiliation: Pharmaceutical Discovery Division, Abbott Laboratories, Abbott Park, IL 60064, USA.
authors.forename: M
authors.initials: M
authors.lastname: Sattler
authors.forename: H
authors.initials: H
authors.lastname: Liang
authors.forename: D
authors.initials: D
authors.lastname: Nettesheim
authors.forename: R P
authors.initials: RP
authors.lastname: Meadows
authors.forename: J E
authors.initials: JE
authors.lastname: Harlan
authors.forename: M
authors.initials: M
authors.lastname: Eberstadt
authors.forename: H S
authors.initials: HS
authors.lastname: Yoon
authors.forename: S B
authors.initials: SB
authors.lastname: Shuker
authors.forename: B S
authors.initials: BS
authors.lastname: Chang
authors.forename: A J
authors.initials: AJ
authors.lastname: Minn
authors.forename: C B
authors.initials: CB
authors.lastname: Thompson
authors.forename: S W
authors.initials: SW
authors.lastname: Fesik
mesh_terms: D000595:Amino Acid Sequence; D017209:Apoptosis; D018360:Crystallography, X-Ray; D019281:Dimerization; D009682:Magnetic Resonance Spectroscopy; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011518:Proto-Oncogene Proteins / Q000737:chemistry* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D017384:Sequence Deletion; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051020:bcl-X Protein
chemical_list: D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051020:bcl-X Protein