Abstract
Cytochrome c(2) (cyt. c(2)) is a major element in electron transfer between redox proteins in bioenergetic membranes. While the interaction between cyt. c(2) and anionic lipids abundant in bioenergetic membranes has been reported, their effect on the shuttling activity of cyt. c(2) remains elusive. Here, the effect of anionic lipids on the interaction and binding of cyt. c(2) to the cytochrome bc(1) complex (bc(1)) is investigated using a combination of molecular dynamics (MD) and Brownian dynamics (BD) simulations. MD is used to generate thermally accessible conformations of cyt. c(2) and membrane-embedded bc(1), which were subsequently used in multireplica BD simulations of diffusion of cyt. c(2) from solution to bc(1), in the presence of various lipids. We show that, counterintuitively, anionic lipids facilitate association of cyt. c(2) with bc(1) by localizing its diffusion to the membrane surface. The observed lipid-mediated bc(1) association is further enhanced by the oxidized state of cyt. c(2), in line with its physiological function. This lipid-mediated enhancement is salinity-dependent, and anionic lipids can disrupt cyt. c(2)-bc(1) interaction at nonphysiological salt levels. Our data highlight the importance of the redox state of cyt. c(2), the lipid composition of the chromatophore membrane, and the salinity of the chromatophore in regulating the efficiency of the electron shuttling process mediated by cyt. c(2). The conclusions can be extrapolated to mitochondrial systems and processes, or any bioenergetic membrane, given the structural similarity between cyt. c(2) and bc(1) and their mitochondrial counterparts.