Abstract
A peptide corresponding to the BH3 region of the proapoptotic protein, BID, could be bound in the cleft of the antiapoptotic protein, BCL-w. This binding induced major conformational rearrangements in both the peptide and protein components of the complex and led to the displacement and unfolding of the BCL-w C-terminal alpha-helix. The structure of BCL-w with a bound BID-BH3 peptide was determined using NMR spectroscopy and molecular docking. These studies confirmed that a region of 16 residues of the BID-BH3 peptide is responsible for its strong binding to BCL-w and BCL-x(L). The interactions of BCL-w and the BID-BH3 peptide complex with dodecylphosphocholine micelles were characterized and showed that the conformational change of BCL-w upon lipid binding occurred at the same time as the release and unfolding of the BH3 peptide.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis Regulatory Proteins
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BH3 Interacting Domain Death Agonist Protein / chemistry*
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BH3 Interacting Domain Death Agonist Protein / metabolism
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Computer Simulation
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Electron Spin Resonance Spectroscopy
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Humans
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Mice
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Micelles*
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Models, Molecular
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Nuclear Magnetic Resonance, Biomolecular
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Peptide Fragments / metabolism
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Phospholipids / chemistry*
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Protein Conformation / drug effects
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Proteins / chemistry*
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Proteins / metabolism
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-bcl-2 / physiology
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bcl-X Protein / metabolism
Substances
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Apoptosis Regulatory Proteins
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BCL2L2 protein, human
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BH3 Interacting Domain Death Agonist Protein
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BID protein, human
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Bax protein (53-86)
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Bcl2l1 protein, mouse
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Micelles
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Peptide Fragments
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Phospholipids
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Proteins
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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bcl-X Protein