Cytochrome c (cyt c) is a heme protein which transfers electrons in a monomeric state from cytochrome bc1 complex to cytochrome c oxidase. It has been well known that cyt c can from polymers and lose its electron transfer function. Recently, Hirota et al. showed that cyt c forms polymers by successive domain swapping, where the C-terminal helices are replaced by the corresponding helices of other cyt c proteins. However, the mechanism of domain swapping of cyt c is still unclear. In the present study, we investigate the thermodynamic stability of the domain swapped dimer of cyt c in aqueous solution by using the molecular dynamics (MD) simulation and the three-dimensional reference interaction-site model (3D-RISM) theory. We find that the domain swapped dimer of cyt c is slightly less stable compared with the monomer, which is consistent with the experimental result. We also find that conformation energy and structural entropy of protein contribute the dimer instability, whereas solvation free energy contributes to the dimer stability. Furthermore, the decomposition analysis shows that several positively and negatively charged residues play important roles in the stabilization and destabilization of the dimer, respectively. The present result demonstrates the importance of solvent effect on the domain-swapped oligomer formation of cyt c. Furthermore, it is also known that the formation of dimer greatly depends on the nature of the anion. We also discuss the anion effects on the stability of the dimer.

Anion effects on oligomer formation of cytochrome c with MD simulation and 3D-RISM theory

255th National Meeting (2018)

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