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. 2011 Apr 18;6(4):e18329.
doi: 10.1371/journal.pone.0018329.

The anti-apoptotic Bcl-x(L) protein, a new piece in the puzzle of cytochrome c interactome

Ivano Bertini  1 , Soizic Chevance, Rebecca Del Conte, Daniela Lalli, Paola Turano
Affiliations

The anti-apoptotic Bcl-x(L) protein, a new piece in the puzzle of cytochrome c interactome

Ivano Bertini et al. PLoS One. .

Abstract

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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Cytochrome c−Bcl-xL adduct.
Residues on cytochrome c (gray and cyan) and Bcl-xL (pink and violet) involved in intermolecular contacts in our structural model. They have been mapped on the lowest energy structure of our cluster of 128 conformers.
Figure 2
Figure 2. Bcl-xL interaction areas.
Ribbon representation of the structure of Bcl-xL: the putative transmembrane hydrophobic tail points towards the bottom part of the picture. Residues involved in contacts with cytochrome c are represented as blue spheres. The Bak peptide is shown in magenta and its interaction area has only a few contact points with that defined for cytochrome c.
Figure 3
Figure 3. Hydrophobic and electrostatic contacts in cytochrome c complexes.
Residues involved in hydrophobic (blue spheres) and in electrostatic/H-bond (red spheres) interactions are shown for: (A) human cytochrome c and Bcl-xL, (B) cytochrome c552 and cytochrome c oxidase, (C) S. cerevisiae cytochrome c and cytochrome bc1, (D) S. cerevisiae cytochrome c and cytochrome c peroxidase adducts. In the four panels, cytochrome c is represented with an orientation where the “loop face” points towards the observer.
See this image and copyright information in PMC

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