Abstract
ATP synthases produce ATP by rotary catalysis, powered by the electrochemical proton gradient across the membrane. Understanding this fundamental process requires an atomic model of the proton pathway. We determined the structure of an intact mitochondrial ATP synthase dimer by electron cryo-microscopy at near-atomic resolution. Charged and polar residues of the a-subunit stator define two aqueous channels, each spanning one half of the membrane. Passing through a conserved membrane-intrinsic helix hairpin, the lumenal channel protonates an acidic glutamate in the c-ring rotor. Upon ring rotation, the protonated glutamate encounters the matrix channel and deprotonates. An arginine between the two channels prevents proton leakage. The steep potential gradient over the sub-nm inter-channel distance exerts a force on the deprotonated glutamate, resulting in net directional rotation.
Highlights
Mitochondrial ATP synthase uses the energy of the electrochemical proton gradient across the inner mitochondrial membrane to produce ATP from ADP and phosphate by rotary catalysis (Abrahams et al, 1994; Gresser et al, 1982)
Understanding how this fundamental process generates rotary force requires an atomic model of the proton pathway
We determined the structure of a 1.6 MDa mitochondrial F1Fo ATP synthase dimer by single-particle electron cryo-microscopy
Summary
Mitochondrial ATP synthase uses the energy of the electrochemical proton gradient across the inner mitochondrial membrane to produce ATP from ADP and phosphate by rotary catalysis (Abrahams et al, 1994; Gresser et al, 1982). Rotation is driven by protons flowing down the membrane gradient through the Fo subcomplex. Understanding how this fundamental process generates rotary force requires an atomic model of the proton pathway. The recent cryo-EM structure of the Fo subcomplex dimer isolated from yeast mitochondria (Guo et al, 2017) indicated the positions of key residues in the proton pathway. Our structure reveals two prominent aqueous channels, each spanning one half of the membrane, that conduct protons to and from the conserved glutamates in the rotor ring. Protonation and deprotonation of these glutamates drives ring rotation and ATP synthesis
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