Abstract
We report the solution structure of BID, an intracellular cross-talk agent that can amplify FAS/TNF apoptotic signal through the mitochondria death pathway after Caspase 8 cleavage. BID contains eight alpha helices where two central hydrophobic helices are surrounded by six amphipathic ones. The fold resembles poreforming bacterial toxins and shows similarity to BCL-XL although sequence homology to BCL-XL is limited to the 16-residue BH3 domain. Furthermore, we modeled a complex of BCL-XL and BID by aligning the BID and BAK BH3 motifs in the known BCL-XL-BAK BH3 complex. Additionally, we show that the overall structure of BID is preserved after cleavage by Caspase 8. We propose that BID has both BH3 domain-dependent and -independent modes of action in inducing mitochondrial damage.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Apoptosis / physiology*
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BH3 Interacting Domain Death Agonist Protein
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Carrier Proteins / chemistry*
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Carrier Proteins / physiology
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Caspase 8
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Caspase 9
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Caspases / metabolism
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Dimerization
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Enzyme Activation
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Humans
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Magnetic Resonance Spectroscopy
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Mitochondria / physiology
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Models, Molecular
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Molecular Sequence Data
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Protein Conformation*
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Protein Multimerization
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Protein Structure, Tertiary
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Proto-Oncogene Proteins c-bcl-2 / chemistry
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Recombinant Fusion Proteins / chemistry
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Sequence Alignment
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Sequence Homology, Amino Acid
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Signal Transduction / physiology*
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Solutions
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Structure-Activity Relationship
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bcl-X Protein
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fas Receptor / physiology
Substances
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BCL2L1 protein, human
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BH3 Interacting Domain Death Agonist Protein
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BID protein, human
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Carrier Proteins
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Proto-Oncogene Proteins c-bcl-2
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Recombinant Fusion Proteins
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Solutions
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bcl-X Protein
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fas Receptor
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CASP8 protein, human
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CASP9 protein, human
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Caspase 8
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Caspase 9
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Caspases