biostudies-literatureKishikawa JIMEXT | Japan Society for the Promotion of ScienceMEXT | Japan Society for the Promotion of Science (JSPS)Takeda Science Foundation9883https://www.ebi.ac.uk/biostudies/studies/S-EPMC11579504biostudies-literatureUnknown15(1)ATP synthases play a crucial role in energy production by utilizing the proton motive force (pmf) across the membrane to rotate their membrane-embedded rotor c-ring, and thus driving ATP synthesis in the hydrophilic catalytic hexamer. However, the mechanism of how pmf converts into c-ring rotation remains unclear. This study presents a 2.8 Å cryo-EM structure of the V_o domain of V/A-ATPase from Thermus thermophilus, revealing precise orientations of glutamate (Glu) residues in the c₁₂-ring. Three Glu residues face a water channel, with one forming a salt bridge with the Arginine in the stator (a/Arg). Molecular dynamics (MD) simulations show that protonation of specific Glu residues triggers unidirectional Brownian motion of the c₁₂-ring towards ATP synthesNature communicationsRotary mechanism of the prokaryotic V<sub>o</sub> motor driven by proton motive force.PMC1157950423H0245320K0651422H02595Kishikawa JINakano AMitsuoka KYokoyama KOkazaki KIKato TNishida YfalseRotary mechanism of the prokaryotic V<sub>o</sub> motor driven by proton motive force.ATP synthases play a crucial role in energy production by utilizing the proton motive force (pmf) across the membrane to rotate their membrane-embedded rotor c-ring, and thus driving ATP synthesis in the hydrophilic catalytic hexamer. However, the mechanism of how pmf converts into c-ring rotation remains unclear. This study presents a 2.8 Å cryo-EM structure of the V_o domain of V/A-ATPase from Thermus thermophilus, revealing precise orientations of glutamate (Glu) residues in the c₁₂-ring. Three Glu residues face a water channel, with one forming a salt bridge with the Arginine in the stator (a/Arg). Molecular dynamics (MD) simulations show that protonation of specific Glu residues triggers unidirectional Brownian motion of the c₁₂-ring towards ATP synthes2024-01-01T00:00:00Z2024 Nov2026-06-03T01:07:30.966Z2025-04-04T12:01:50.553ZS-EPMC115795043956748710.1038/s41467-024-53504-x