Rotary mechanism of the prokaryotic Vo motor driven by proton motive force

Abstract 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 r...

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Main Authors: Jun-ichi Kishikawa, Yui Nishida, Atsuki Nakano, Takayuki Kato, Kaoru Mitsuoka, Kei-ichi Okazaki, Ken Yokoyama
Format: Article
Language:English
Published: Nature Portfolio 2024-11-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-024-53504-x
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author Jun-ichi Kishikawa
Yui Nishida
Atsuki Nakano
Takayuki Kato
Kaoru Mitsuoka
Kei-ichi Okazaki
Ken Yokoyama
author_facet Jun-ichi Kishikawa
Yui Nishida
Atsuki Nakano
Takayuki Kato
Kaoru Mitsuoka
Kei-ichi Okazaki
Ken Yokoyama
author_sort Jun-ichi Kishikawa
collection DOAJ
description Abstract 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 Vo domain of V/A-ATPase from Thermus thermophilus, revealing precise orientations of glutamate (Glu) residues in the c 12-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 c 12-ring towards ATP synthesis. When the key Glu remains unprotonated, the salt bridge persists, blocking rotation. These findings suggest that asymmetry in the protonation of c/Glu residues biases c 12-ring movement, facilitating rotation and ATP synthesis.
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spelling doaj-art-022cd08ce6ee492fb5770ca374c5fabf2024-11-24T12:34:14ZengNature PortfolioNature Communications2041-17232024-11-0115111210.1038/s41467-024-53504-xRotary mechanism of the prokaryotic Vo motor driven by proton motive forceJun-ichi Kishikawa0Yui Nishida1Atsuki Nakano2Takayuki Kato3Kaoru Mitsuoka4Kei-ichi Okazaki5Ken Yokoyama6Department of Molecular Biosciences, Kyoto Sangyo University, Kamigamo-Motoyama, Kita-kuDepartment of Molecular Biosciences, Kyoto Sangyo University, Kamigamo-Motoyama, Kita-kuDepartment of Molecular Biosciences, Kyoto Sangyo University, Kamigamo-Motoyama, Kita-kuInstitute for Protein Research, Osaka University, 3-2 Yamadaoka, SuitaResearch Center for Ultra-High Voltage Electron Microscopy, Osaka UniversityResearch Center for Computational Science, Institute for Molecular Science, National Institutes of Natural SciencesDepartment of Molecular Biosciences, Kyoto Sangyo University, Kamigamo-Motoyama, Kita-kuAbstract 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 Vo domain of V/A-ATPase from Thermus thermophilus, revealing precise orientations of glutamate (Glu) residues in the c 12-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 c 12-ring towards ATP synthesis. When the key Glu remains unprotonated, the salt bridge persists, blocking rotation. These findings suggest that asymmetry in the protonation of c/Glu residues biases c 12-ring movement, facilitating rotation and ATP synthesis.https://doi.org/10.1038/s41467-024-53504-x
spellingShingle Jun-ichi Kishikawa
Yui Nishida
Atsuki Nakano
Takayuki Kato
Kaoru Mitsuoka
Kei-ichi Okazaki
Ken Yokoyama
Rotary mechanism of the prokaryotic Vo motor driven by proton motive force
Nature Communications
title Rotary mechanism of the prokaryotic Vo motor driven by proton motive force
title_full Rotary mechanism of the prokaryotic Vo motor driven by proton motive force
title_fullStr Rotary mechanism of the prokaryotic Vo motor driven by proton motive force
title_full_unstemmed Rotary mechanism of the prokaryotic Vo motor driven by proton motive force
title_short Rotary mechanism of the prokaryotic Vo motor driven by proton motive force
title_sort rotary mechanism of the prokaryotic vo motor driven by proton motive force
url https://doi.org/10.1038/s41467-024-53504-x
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