Structure of Bcl-xL-Bak peptide complex: recognition between regulators of apoptosis.
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.
Sattler
M
M
Pharmaceutical Discovery Division, Abbott Laboratories, Abbott Park, IL 60064, USA.
Liang
H
H
Nettesheim
D
D
Meadows
R P
RP
Harlan
J E
JE
Eberstadt
M
M
Yoon
H S
HS
Shuker
S B
SB
Chang
B S
BS
Minn
A J
AJ
Thompson
C B
CB
Fesik
S W
SW
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
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