TY  - INPR
A1  - Lasham, Jonathan
A1  - Haapanen, Outi
A1  - Zickermann, Volker
A1  - Sharma, Vivek
T1  - Tunnel dynamics of quinone derivatives and its coupling to protein conformational rearrangements in respiratory complex I
T2  - bioRxiv
N2  - 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.
Y1  - 2022
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/73074
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-730742
IS  - 2022.06.21.497056
ER  -