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.