Mechanism of proton-powered c-ring rotation in a mitochondrial ATP synthase.

Autor: Blanc FEC; Department of Theoretical Biophysics, Max Planck Institute of Biophysics, Frankfurt am Main 60438, Germany., Hummer G; Department of Theoretical Biophysics, Max Planck Institute of Biophysics, Frankfurt am Main 60438, Germany.; Institute for Biophysics, Goethe University Frankfurt, Frankfurt am Main 60438, Germany.
Jazyk: angličtina
Zdroj: Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2024 Mar 12; Vol. 121 (11), pp. e2314199121. Date of Electronic Publication: 2024 Mar 07.
DOI: 10.1073/pnas.2314199121
Abstrakt: Proton-powered c-ring rotation in mitochondrial ATP synthase is crucial to convert the transmembrane protonmotive force into torque to drive the synthesis of adenosine triphosphate (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.
Competing Interests: Competing interests statement:The authors declare no competing interest.
Databáze: MEDLINE