title: A Brownian dynamics study: the effect of a membrane environment on an electron transfer system.
abstract: During the past few years, three-dimensional crystal structures of many of the important integral membrane proteins responsible for the bioenergetic processes of photosynthesis and respiration have been determined. Moreover, a few crystal structures of protein-protein complexes have become available that characterize the interaction between those membrane proteins and the electron carrier protein cytochrome c. Here, we address the association kinetics for binding of cytochrome c to cytochrome c oxidase (COX) from Paracoccus denitrificans by Brownian dynamics simulations. The effects of ionic strength and protein mutations were studied for two different cytochrome c species: the positively charged, dipolar horse heart cytochrome c and the negatively charged physiological electron transfer partner cytochrome c(552). We studied association toward "naked" COX and toward membrane-embedded COX where the membrane is represented as an uncharged DPPC bilayer modeled in atomistic detail. For the nonnatural association toward "naked" COX, the association rates are >100 times larger for horse heart cytochrome c than for cytochrome c(552). Interestingly, the presence of the lipid bilayer leads to a dramatic decrease of the association rate of horse heart cytochrome c, but slightly enhances association of cytochrome c(552), leading to very similar association rates of both proteins to membrane-embedded COX. This finding from computational modeling studies may reflect the optimization of surface patches and of the total net charge on electron transfer pairs in nature.
authors.affiliation: Max Planck Institute of Biophysics, Frankfurt, Germany.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Flöck
authors.forename: Volkhard
authors.initials: V
authors.lastname: Helms
mesh_terms: D000818:Animals; D003198:Computer Simulation; D003574:Cytochrome c Group / Q000378:metabolism*; D004579:Electron Transport / Q000502:physiology; D003576:Electron Transport Complex IV / Q000378:metabolism*; D004734:Energy Metabolism / Q000502:physiology*; D006736:Horses; D008051:Lipid Bilayers / Q000378:metabolism*; D008566:Membranes / Q000378:metabolism*; D008958:Models, Molecular; D010231:Paracoccus denitrificans / Q000201:enzymology
chemical_list: D003574:Cytochrome c Group; D008051:Lipid Bilayers; C076615:cytochrome c''; D003576:Electron Transport Complex IV