The Anti-Apoptotic Bcl-x(L) Protein, a New Piece in the Puzzle of Cytochrome C Interactome

A structural model of the adduct between human cytochrome c and the human anti-apoptotic protein Bcl-x(L), which defines the protein-protein interaction surface, was obtained from solution NMR chemical shift perturbation data. The atomic level information reveals key intermolecular contacts identifying new potentially druggable areas on cytochrome c and Bcl-x(L). Involvement of residues on cytochrome c other than those in its complexes with electron transfer partners is apparent. Key differences in the contact area also exist between the Bcl-x(L) adduct with the Bak peptide and that with cytochrome c. The present model provides insights to the mechanism by which cytochrome c translocated to cytosol can be intercepted, so that the apoptosome is not assembled.