Abstract
Apoptosis is held in check by prosurvival proteins of the Bcl-2 family. The distantly related BH3-only proteins bind to and antagonize them, thereby promoting apoptosis. Whereas binding of the BH3-only protein Noxa to prosurvival Mcl-1 induces Mcl-1 degradation by the proteasome, binding of another BH3-only ligand, Bim, elevates Mcl-1 protein levels. We compared the three-dimensional structures of the complexes formed between BH3 peptides of both Bim and Noxa, and we show that a discrete C-terminal sequence of the Noxa BH3 is necessary to instigate Mcl-1 degradation.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Apoptosis / genetics*
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Apoptosis Regulatory Proteins / metabolism
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Bcl-2-Like Protein 11
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Crystallography
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Humans
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Membrane Proteins / metabolism
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Mice
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Models, Molecular*
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Molecular Sequence Data
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Multiprotein Complexes / chemistry
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Multiprotein Complexes / metabolism*
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Myeloid Cell Leukemia Sequence 1 Protein
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Neoplasm Proteins / chemistry
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Neoplasm Proteins / metabolism*
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Nuclear Magnetic Resonance, Biomolecular
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Protein Structure, Tertiary*
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-bcl-2 / chemistry
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Proto-Oncogene Proteins c-bcl-2 / metabolism*
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Recombinant Fusion Proteins / chemistry
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Recombinant Fusion Proteins / metabolism*
Substances
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Apoptosis Regulatory Proteins
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BCL2L11 protein, human
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Bcl-2-Like Protein 11
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Bcl2l11 protein, mouse
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Mcl1 protein, mouse
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Membrane Proteins
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Multiprotein Complexes
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Myeloid Cell Leukemia Sequence 1 Protein
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Neoplasm Proteins
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PMAIP1 protein, human
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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Recombinant Fusion Proteins
Associated data
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PDB/2JM6
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PDB/2NL9
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PDB/2NLA