Structural model of the BCL-w-BID peptide complex and its interactions with phospholipid micelles

Biochemistry. 2006 Feb 21;45(7):2250-6. doi: 10.1021/bi052332s.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins
  • BH3 Interacting Domain Death Agonist Protein / chemistry*
  • BH3 Interacting Domain Death Agonist Protein / metabolism
  • Computer Simulation
  • Electron Spin Resonance Spectroscopy
  • Humans
  • Mice
  • Micelles*
  • Models, Molecular
  • Nuclear Magnetic Resonance, Biomolecular
  • Peptide Fragments / metabolism
  • Phospholipids / chemistry*
  • Protein Conformation / drug effects
  • Proteins / chemistry*
  • Proteins / metabolism
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / physiology
  • bcl-X Protein / metabolism

Substances

  • Apoptosis Regulatory Proteins
  • BCL2L2 protein, human
  • BH3 Interacting Domain Death Agonist Protein
  • BID protein, human
  • Bax protein (53-86)
  • Bcl2l1 protein, mouse
  • Micelles
  • Peptide Fragments
  • Phospholipids
  • Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-X Protein

Associated data

  • PDB/1ZY3