Mechanism of proton-powered c-ring rotation in a mitochondrial ATP synthase
- Proton-powered c-ring rotation in mitochondrial ATP synthase is crucial to convert the transmembrane protonmotive force into torque to drive the synthesis of ATP. Capitalizing on recent cryo-EM structures, we aim at a structural and energetic understanding of how functional directional rotation is achieved. We performed multi-microsecond atomistic simulations to determine the free energy profiles along the c-ring rotation angle before and after the arrival of a new proton. Our results reveal that rotation proceeds by dynamic sliding of the ring over the a-subunit surface, during which interactions with conserved polar residues stabilize distinct intermediates. Ordered water chains line up for a Grotthuss-type proton transfer in one of these intermediates. After proton transfer, a high barrier prevents backward rotation and an overall drop in free energy favors forward rotation, ensuring the directionality of c-ring rotation required for the thermodynamically disfavored ATP synthesis. The essential arginine of the a-subunit stabilizes the rotated configuration through a salt-bridge with the c-ring. Overall, we describe a complete mechanism for the rotation step of the ATP synthase rotor, thereby illuminating a process critical to all life at atomic resolution.
Author: | Florian E. C. BlancORCiD, Gerhard HummerORCiD |
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URN: | urn:nbn:de:hebis:30:3-754074 |
URL: | https://www.biorxiv.org/content/10.1101/2023.08.11.551925v1 |
DOI: | https://doi.org/10.1101/2023.08.11.551925 |
Parent Title (English): | bioRxiv |
Document Type: | Preprint |
Language: | English |
Date of Publication (online): | 2023/08/14 |
Date of first Publication: | 2023/08/14 |
Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Release Date: | 2023/09/04 |
Issue: | 2023.08.11.551925 Version 1 |
Edition: | Version 1 |
Page Number: | 32 |
HeBIS-PPN: | 511592264 |
Institutes: | Physik |
Angeschlossene und kooperierende Institutionen / MPI für Biophysik | |
Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
Sammlungen: | Universitätspublikationen |
Licence (German): | Creative Commons - CC BY-NC - Namensnennung - Nicht kommerziell 4.0 International |