the anti-apoptotic bcl-xl protein, a new piece in the puzzle of cytochrome c interactome抗凋亡bcl-xl蛋白,细胞色素c的新拼图的interactome.pdf

The Anti-Apoptotic Bcl-xL Protein, a New Piece in the Puzzle of Cytochrome C Interactome 1,2 1 1 1,2 1,2 Ivano Bertini *, Soizic Chevance , Rebecca Del Conte , Daniela Lalli , Paola Turano 1 Magnetic Resonance Center (CERM), University of Florence, Sesto Fiorentino, Florence, Italy, 2 Department of Chemistry, University of Florence, Sesto Fiorentino, Florence, Italy Abstract A structural model of the adduct between human cytochrome c and the human anti-apoptotic protein Bcl-x , which defines L 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-xL. 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-xL 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. Citation: Bertini I, Chevance S, Del Conte R, Lalli D, Turano P (2011) The Anti-Apoptotic Bcl-xL Protein, a New Piece in the Puzzle of Cytochrome C Interactome. PLoS ONE 6(4): e18329. doi:10.1371/journal.pone.0018329 Editor: Pierandrea Temussi, University of Naples, Italy Received December 30, 2010; Accepted February 25, 2011; Published April 18, 2011 Copyright: 2011 Bertini et al. This is an open-access article distributed u