Structure of Bax: coregulation of dimer formation and intracellular localization.
Apoptosis is stimulated by the insertion of Bax from the cytosol into mitochondrial membranes. The solution structure of Bax, including the putative transmembrane domain at the C terminus, was determined in order to understand the regulation of its subcellular location. Bax consists of 9 alpha helices where the assembly of helices alpha1 through alpha 8 resembles that of the apoptosis inhibitor, Bcl-x(L). The C-terminal alpha 9 helix occupies the hydrophobic pocket proposed previously to mediate heterodimer formation and bioactivity of opposing members of the Bcl-2 family. The Bax structure shows that the orientation of helix alpha 9 provides simultaneous control over its mitochondrial targeting and dimer formation.
Suzuki
M
M
Biochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Youle
R J
RJ
Tjandra
N
N
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D019556:COS Cells; D002451:Cell Compartmentation; D003902:Detergents / Q000494:pharmacology; D019281:Dimerization; D005960:Glucosides / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000737:chemistry* / Q000187:drug effects / Q000302:isolation & purification; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000737:chemistry; D011993:Recombinant Fusion Proteins / Q000302:isolation & purification; D017386:Sequence Homology, Amino Acid; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
C494826:BAX protein, human; C494811:BCL2L1 protein, human; D003902:Detergents; D005960:Glucosides; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011993:Recombinant Fusion Proteins; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; C018619:octyl-beta-D-glucoside