Structural model of the BCL-w-BID peptide complex and its interactions with phospholipid micelles.
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.
Denisov
Alexey Yu
AY
Department of Biochemistry, McGill University, Montreal, Quebec H3G 1Y6, Canada.
Chen
Gang
G
Sprules
Tara
T
Moldoveanu
Tudor
T
Beauparlant
Pierre
P
Gehring
Kalle
K
D000818:Animals; D051017:Apoptosis Regulatory Proteins; D051023:BH3 Interacting Domain Death Agonist Protein / Q000737:chemistry* / Q000378:metabolism; D003198:Computer Simulation; D004578:Electron Spin Resonance Spectroscopy; D006801:Humans; D051379:Mice; D008823:Micelles; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000378:metabolism; D010743:Phospholipids / Q000737:chemistry*; D011487:Protein Conformation / Q000187:drug effects; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology; D051020:bcl-X Protein / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; C491073:BCL2L2 protein, human; D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; C474007:Bax protein (53-86); C494812:Bcl2l1 protein, mouse; D008823:Micelles; D010446:Peptide Fragments; D010743:Phospholipids; D011506:Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein