Electron Tunneling in Respiratory Complex I

Abstract

NADH:ubiquinone oxidoreductase (complex I) plays a central role in the respiratory electron transport chain by coupling the transfer of electrons from NADH to ubiquinone to proton pumping across the membrane. Until now, the atomistic details of electron transfer have remained unknown. In this study, electron tunneling along seven Fe/S clusters in complex I is examined in atomistic resolution by using the tunneling current theory and computer simulations [1]. Distinct electron tunneling pathways between neighboring Fe/S clusters are identified; the pathways primarily consist of two cysteine ligands and one additional key residue. The identified key residues are further characterized by sensitivity of electron transfer rates to their mutations, examined in simulations and their conservation among complex I homologues. Internal water between protein subunits is identified as an essential mediator enhancing drastically the overall electron transfer rate to achieve the physiologically significant value. With the water included, negative slope of the distance dependence of the electron transfer rates becomes close to a typical 1.4 in natural logarithm. The unusual electronic structure properties of Fe/S clusters in complex I explain their remarkable efficiency of electron transfer. [1] T.Hayashi, A.A.Stuchebrukhov, Proc. Natl. Acad. Sci. U.S.A. 107, 19157