title: Structure and conformational states of the bovine mitochondrial ATP synthase by cryo-EM.
abstract: Adenosine triphosphate (ATP), the chemical energy currency of biology, is synthesized in eukaryotic cells primarily by the mitochondrial ATP synthase. ATP synthases operate by a rotary catalytic mechanism where proton translocation through the membrane-inserted FO region is coupled to ATP synthesis in the catalytic F1 region via rotation of a central rotor subcomplex. We report here single particle electron cryomicroscopy (cryo-EM) analysis of the bovine mitochondrial ATP synthase. Combining cryo-EM data with bioinformatic analysis allowed us to determine the fold of the a subunit, suggesting a proton translocation path through the FO region that involves both the a and b subunits. 3D classification of images revealed seven distinct states of the enzyme that show different modes of bending and twisting in the intact ATP synthase. Rotational fluctuations of the c8-ring within the FO region support a Brownian ratchet mechanism for proton-translocation-driven rotation in ATP synthases.
authors.affiliation: The Hospital for Sick Children Research Institute, Toronto, Canada.|Department of Medical Biophysics, The University of Toronto, Ontario, Canada.
authors.forename: Anna
authors.initials: A
authors.lastname: Zhou
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States.
authors.forename: Alexis
authors.identifier: http://orcid.org/0000-0002-3343-9621
authors.initials: A
authors.lastname: Rohou
authors.affiliation: The Hospital for Sick Children Research Institute, Toronto, Canada.|Department of Medical Biophysics, The University of Toronto, Ontario, Canada.
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Schep
authors.affiliation: MRC Mitochondrial Biology Unit, Cambridge, United Kingdom.
authors.forename: John V
authors.initials: JV
authors.lastname: Bason
authors.affiliation: MRC Mitochondrial Biology Unit, Cambridge, United Kingdom.
authors.forename: Martin G
authors.initials: MG
authors.lastname: Montgomery
authors.affiliation: MRC Mitochondrial Biology Unit, Cambridge, United Kingdom.
authors.forename: John E
authors.initials: JE
authors.lastname: Walker
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States.
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Grigorieff
authors.affiliation: The Hospital for Sick Children Research Institute, Toronto, Canada.|Department of Medical Biophysics, The University of Toronto, Ontario, Canada.|Department of Biochemistry, The University of Toronto, Ontario, Canada.
authors.forename: John L
authors.initials: JL
authors.lastname: Rubinstein
mesh_terms: D000818:Animals; D002417:Cattle; D019295:Computational Biology; D020285:Cryoelectron Microscopy; D021621:Imaging, Three-Dimensional; D025261:Mitochondrial Proton-Translocating ATPases / Q000737:chemistry* / Q000235:genetics; D008958:Models, Molecular; D011487:Protein Conformation; D017510:Protein Folding
chemical_list: D025261:Mitochondrial Proton-Translocating ATPases
keywords: ATP synthase; biochemistry; biophysics; bovine; coevolution; cryo-EM; evolutionary covariance; structural biology; structure