|Title||Horizontal membrane-intrinsic α-helices in the stator a-subunit of an F-type ATP synthase.|
|Publication Type||Journal Article|
|Year of Publication||2015|
|Authors||Allegretti, M, Klusch, N, Mills, DJ, Vonck, J, Kühlbrandt, W, Davies, KM|
|Date Published||2015 May 14|
|Keywords||Adenosine 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.