title: Structure of a Complete ATP Synthase Dimer Reveals the Molecular Basis of Inner Mitochondrial Membrane Morphology.
abstract: We determined the structure of a complete, dimeric F1Fo-ATP synthase from yeast Yarrowia lipolytica mitochondria by a combination of cryo-EM and X-ray crystallography. The final structure resolves 58 of the 60 dimer subunits. Horizontal helices of subunit a in Fo wrap around the c-ring rotor, and a total of six vertical helices assigned to subunits a, b, f, i, and 8 span the membrane. Subunit 8 (A6L in human) is an evolutionary derivative of the bacterial b subunit. On the lumenal membrane surface, subunit f establishes direct contact between the two monomers. Comparison with a cryo-EM map of the F1Fo monomer identifies subunits e and g at the lateral dimer interface. They do not form dimer contacts but enable dimer formation by inducing a strong membrane curvature of ∼100°. Our structure explains the structural basis of cristae formation in mitochondria, a landmark signature of eukaryotic cell morphology.
authors.affiliation: Department of Structural Biology, Max Planck Institute of Biophysics, Max-von-Laue-Str. 3, 60438 Frankfurt am Main, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Hahn
authors.affiliation: Department of Structural Biology, Max Planck Institute of Biophysics, Max-von-Laue-Str. 3, 60438 Frankfurt am Main, Germany.
authors.forename: Kristian
authors.initials: K
authors.lastname: Parey
authors.affiliation: Institute of Biochemistry, Goethe University Frankfurt, Max-von-Laue-Str. 9, 60438 Frankfurt am Main, Germany.
authors.forename: Maike
authors.initials: M
authors.lastname: Bublitz
authors.affiliation: Department of Structural Biology, Max Planck Institute of Biophysics, Max-von-Laue-Str. 3, 60438 Frankfurt am Main, Germany.
authors.forename: Deryck J
authors.initials: DJ
authors.lastname: Mills
authors.affiliation: Institute of Biochemistry II, Medical School, Goethe University Frankfurt, Max-von-Laue-Str. 9, 60438 Frankfurt am Main, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Zickermann
authors.affiliation: Department of Structural Biology, Max Planck Institute of Biophysics, Max-von-Laue-Str. 3, 60438 Frankfurt am Main, Germany.
authors.forename: Janet
authors.initials: J
authors.lastname: Vonck
authors.affiliation: Department of Structural Biology, Max Planck Institute of Biophysics, Max-von-Laue-Str. 3, 60438 Frankfurt am Main, Germany. Electronic address: werner.kuehlbrandt@biophys.mpg.de.
authors.forename: Werner
authors.initials: W
authors.lastname: Kühlbrandt
authors.affiliation: Department of Structural Biology, Max Planck Institute of Biophysics, Max-von-Laue-Str. 3, 60438 Frankfurt am Main, Germany. Electronic address: t.meier@imperial.ac.uk.
authors.forename: Thomas
authors.initials: T
authors.lastname: Meier
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D002384:Catalysis; D020285:Cryoelectron Microscopy; D018360:Crystallography, X-Ray; D005656:Fungal Proteins / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D008928:Mitochondria / Q000201:enzymology* / Q000648:ultrastructure; D051336:Mitochondrial Membranes / Q000201:enzymology* / Q000648:ultrastructure; D025261:Mitochondrial Proton-Translocating ATPases / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D008958:Models, Molecular; D000072756:Protein Conformation, alpha-Helical; D055503:Protein Multimerization; D021122:Protein Subunits; D013329:Structure-Activity Relationship; D025062:Yarrowia / Q000201:enzymology* / Q000648:ultrastructure
chemical_list: D005656:Fungal Proteins; D021122:Protein Subunits; D000255:Adenosine Triphosphate; C474451:F1F0-ATP synthase; D025261:Mitochondrial Proton-Translocating ATPases
keywords: F(1)F(o)-ATP synthase dimer; X-ray crystallography; bioenergetics; cryoelectron microscopy; inner membrane morphology; membrane protein complex; mitochondria; rotary ATPase mechanism; yeast Yarrowia lipolytica