RT Journal Article
SR Electronic
T1 Tunnel dynamics of quinone derivatives and its coupling to protein conformational rearrangements in respiratory complex I
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.06.21.497056
DO 10.1101/2022.06.21.497056
A1 Jonathan Lasham
A1 Outi Haapanen
A1 Volker Zickermann
A1 Vivek Sharma
YR 2022
UL http://biorxiv.org/content/early/2022/06/21/2022.06.21.497056.abstract
AB Respiratory complex I in mitochondria and bacteria catalyzes the transfer of electrons from NADH to quinone (Q). The free energy available from the reaction is used to pump protons and to establish a membrane proton electrochemical gradient, which drives ATP synthesis. Even though several high-resolution structures of complex I have been resolved, how Q reduction is linked with proton pumping, remains unknown. Here, microsecond long molecular dynamics (MD) simulations were performed on Yarrowia lipolytica complex I structures where Q molecules have been resolved in the ~30 Å long Q tunnel. MD simulations of several different redox/protonation states of Q reveal the coupling between the Q dynamics and the restructuring of conserved loops and ion pairs. Oxidized quinone stabilizes towards the N2 FeS cluster, a binding mode not previously described in Yarrowia lipolytica complex I structures. On the other hand, reduced (and protonated) species tend to diffuse towards the Q binding sites closer to the tunnel entrance. Mechanistic and physiological relevance of these results are discussed.Competing Interest StatementThe authors have declared no competing interest.