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bioRxiv · 10.1101/2022.06.21.497056

Tunnel dynamics of quinone derivatives and its coupling to protein conformational rearrangements in respiratory complex I

Lasham, J.·Haapanen, O.·Zickermann, V.·Sharma, V.
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Abstract

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 [A] 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.

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Lasham, J., Haapanen, O., Zickermann, V., Sharma, V.. 2022-06-21. Tunnel dynamics of quinone derivatives and its coupling to protein conformational rearrangements in respiratory complex I. https://doi.org/10.1101/2022.06.21.497056

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