Abstract
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.
MeSH terms
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Amino Acid Sequence
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Animals
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Apoptosis
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COS Cells
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Cell Compartmentation
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Detergents / pharmacology
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Dimerization
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Glucosides / pharmacology
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Humans
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Hydrogen-Ion Concentration
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Models, Molecular
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Molecular Sequence Data
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Nuclear Magnetic Resonance, Biomolecular
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Protein Structure, Quaternary
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Protein Structure, Tertiary
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Proto-Oncogene Proteins / chemistry*
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Proto-Oncogene Proteins / drug effects
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Proto-Oncogene Proteins / isolation & purification
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Proto-Oncogene Proteins c-bcl-2 / chemistry
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Recombinant Fusion Proteins / isolation & purification
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Sequence Homology, Amino Acid
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bcl-2-Associated X Protein
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bcl-X Protein
Substances
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BAX protein, human
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BCL2L1 protein, human
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Detergents
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Glucosides
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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Recombinant Fusion Proteins
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bcl-2-Associated X Protein
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bcl-X Protein
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octyl-beta-D-glucoside