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.
Verfasserangaben: | 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 |
Titel des übergeordneten Werkes (Englisch): | bioRxiv |
Dokumentart: | Preprint |
Sprache: | Englisch |
Datum der Veröffentlichung (online): | 21.06.2022 |
Datum der Erstveröffentlichung: | 21.06.2022 |
Veröffentlichende Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Datum der Freischaltung: | 07.06.2023 |
Ausgabe / Heft: | 2022.06.21.497056 |
Seitenzahl: | 29 |
HeBIS-PPN: | 509389031 |
Institute: | Biochemie, Chemie und Pharmazie / Biochemie und Chemie |
DDC-Klassifikation: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
Sammlungen: | Universitätspublikationen |
Lizenz (Deutsch): | Creative Commons - CC BY-NC-ND - Namensnennung - Nicht kommerziell - Keine Bearbeitungen 4.0 International |