Tunnel dynamics of quinone derivatives and its coupling to protein conformational rearrangements in respiratory complex I
- 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.
Author: | Jonathan LashamORCiD, Outi HaapanenORCiD, Volker ZickermannORCiDGND, Vivek SharmaORCiD |
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URN: | urn:nbn:de:hebis:30:3-730742 |
DOI: | https://doi.org/10.1101/2022.06.21.497056 |
Parent Title (English): | bioRxiv |
Document Type: | Preprint |
Language: | English |
Date of Publication (online): | 2022/06/21 |
Date of first Publication: | 2022/06/21 |
Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Release Date: | 2023/06/07 |
Issue: | 2022.06.21.497056 |
Page Number: | 29 |
HeBIS-PPN: | 509389031 |
Institutes: | Biochemie, Chemie und Pharmazie / Biochemie und Chemie |
Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
Sammlungen: | Universitätspublikationen |
Licence (German): | Creative Commons - CC BY-NC-ND - Namensnennung - Nicht kommerziell - Keine Bearbeitungen 4.0 International |