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Subtle Change in the Charge Distribution of Surface Residues May Affect the Secondary Functions of Cytochrome c.

ABSTRACT: Although the primary function of cytochrome c (cyt c) is electron transfer, the protein caries out an additional secondary function involving its interaction with membrane cardiolipin (CDL), its peroxidase activity, and the initiation of apoptosis. Whereas the primary function of cyt c is essentially conserved, its secondary function varies depending on the source of the protein. We report here a detailed experimental and computational study, which aims to understand, at the molecular level, the difference in the secondary functions of cyt c obtained from horse heart (mammalian) and Saccharomyces cerevisiae (yeast). The conformational landscape of cyt c has been found to be heterogeneous, consisting of an equilibrium between the compact and extended conformers as well as the oligomeric species. Because the determination of relative populations of these conformers is difficult to obtain by ensemble measurements, we used fluorescence correlation spectroscopy (FCS), a method that offers single-molecule resolution. The population of different species is found to depend on multiple factors, including the protein source, the presence of CDL and urea, and their concentrations. The complex interplay between the conformational distribution and oligomerization plays a crucial role in the variation of the pre-apoptotic regulation of cyt c observed from different sources. Finally, computational studies reveal that the variation in the charge distribution at the surface and the charge reversal sites may be the key determinant of the conformational stability of cyt c.

SUBMITTER: Paul SS

PROVIDER: S-EPMC4505514 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Subtle Change in the Charge Distribution of Surface Residues May Affect the Secondary Functions of Cytochrome c.

Paul Simanta Sarani SS Sil Pallabi P Haldar Shubhasis S Mitra Samaresh S Chattopadhyay Krishnananda K

The Journal of biological chemistry 20150414 23

Although the primary function of cytochrome c (cyt c) is electron transfer, the protein caries out an additional secondary function involving its interaction with membrane cardiolipin (CDL), its peroxidase activity, and the initiation of apoptosis. Whereas the primary function of cyt c is essentially conserved, its secondary function varies depending on the source of the protein. We report here a detailed experimental and computational study, which aims to understand, at the molecular level, the ...[more]

PMID: 25873393

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Subtle Change in the Charge Distribution of Surface Residues May Affect the Secondary Functions of Cytochrome c.

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Subtle Change in the Charge Distribution of Surface Residues May Affect the Secondary Functions of Cytochrome c.

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