Horizontal membrane-intrinsic α-helices in the stator a-subunit of an F-type ATP synthase.

TitleHorizontal membrane-intrinsic α-helices in the stator a-subunit of an F-type ATP synthase.
Publication TypeJournal Article
Year of Publication2015
AuthorsAllegretti, M, Klusch, N, Mills, DJ, Vonck, J, Kühlbrandt, W, Davies, KM
Date Published2015 May 14
KeywordsAdenosine Triphosphate, Arginine, Chlorophyta, Cryoelectron Microscopy, Glutamic Acid, Histidine, Ion Transport, Lipid Bilayers, Models, Molecular, Protein Multimerization, Protein Structure, Secondary, Protein Subunits, Proton-Translocating ATPases, Protons, Rotation, Water

ATP, the universal energy currency of cells, is produced by F-type ATP synthases, which are ancient, membrane-bound nanomachines. F-type ATP synthases use the energy of a transmembrane electrochemical gradient to generate ATP by rotary catalysis. Protons moving across the membrane drive a rotor ring composed of 8-15 c-subunits. A central stalk transmits the rotation of the c-ring to the catalytic F1 head, where a series of conformational changes results in ATP synthesis. A key unresolved question in this fundamental process is how protons pass through the membrane to drive ATP production. Mitochondrial ATP synthases form V-shaped homodimers in cristae membranes. Here we report the structure of a native and active mitochondrial ATP synthase dimer, determined by single-particle electron cryomicroscopy at 6.2 Å resolution. Our structure shows four long, horizontal membrane-intrinsic α-helices in the a-subunit, arranged in two hairpins at an angle of approximately 70° relative to the c-ring helices. It has been proposed that a strictly conserved membrane-embedded arginine in the a-subunit couples proton translocation to c-ring rotation. A fit of the conserved carboxy-terminal a-subunit sequence places the conserved arginine next to a proton-binding c-subunit glutamate. The map shows a slanting solvent-accessible channel that extends from the mitochondrial matrix to the conserved arginine. Another hydrophilic cavity on the lumenal membrane surface defines a direct route for the protons to an essential histidine-glutamate pair. Our results provide unique new insights into the structure and function of rotary ATP synthases and explain how ATP production is coupled to proton translocation.

Alternate JournalNature
Citation Key10.1038/nature14185
PubMed ID25707805