Abstract
The structure of the dimeric ATP synthase from bovine mitochondria determined in three rotational states by electron cryo-microscopy provides evidence that the proton uptake from the mitochondrial matrix via the proton inlet half channel proceeds via a Grotthus mechanism, and a similar mechanism may operate in the exit half channel. The structure has given information about the architecture and mechanical constitution and properties of the peripheral stalk, part of the membrane extrinsic region of the stator, and how the action of the peripheral stalk damps the side-to-side rocking motions that occur in the enzyme complex during the catalytic cycle. It also describes wedge structures in the membrane domains of each monomer, where the skeleton of each wedge is provided by three α-helices in the membrane domains of the b-subunit to which the supernumerary subunits e, f, and g and the membrane domain of subunit A6L are bound. Protein voids in the wedge are filled by three specifically bound cardiolipin molecules and two other phospholipids. The external surfaces of the wedges link the monomeric complexes together into the dimeric structures and provide a pivot to allow the monomer-monomer interfaces to change during catalysis and to accommodate other changes not related directly to catalysis in the monomer-monomer interface that occur in mitochondrial cristae. The structure of the bovine dimer also demonstrates that the structures of dimeric ATP synthases in a tetrameric porcine enzyme have been seriously misinterpreted in the membrane domains.
Highlights
The structure of the dimeric Adenosine triphosphate (ATP) synthase from bovine mitochondria determined in three rotational states by electron cryomicroscopy provides evidence that the proton uptake from the mitochondrial matrix via the proton inlet half channel proceeds via a Grotthus mechanism, and a similar mechanism may operate in the exit half channel
Each monomeric unit in the dimeric bovine enzyme described here is an assembly of 28 polypeptide chains of 17 different kinds, organized into a spherical catalytic globular domain that extends from the inner mitochondrial membrane (IMM) into the mitochondrial matrix, attached to an intrinsic membrane domain by a central stalk and a peripheral stalk (PS) [4]
The rigid rod is connected to the membrane domain of the stator by a hinge at residues 73 to 90 of bH3, which remains relatively immobile as bH3 and bH4, and associated subunits d, F6, and oligomycin sensitivity conferral protein (OSCP) are displaced laterally by 9.9 and 13.1 Å in states 1 and 3, respectively, measured relative to state 2 (SI Appendix, Fig. S23)
Summary
The structure of the dimeric ATP synthase from bovine mitochondria determined in three rotational states by electron cryomicroscopy provides evidence that the proton uptake from the mitochondrial matrix via the proton inlet half channel proceeds via a Grotthus mechanism, and a similar mechanism may operate in the exit half channel. The atomic models of the dimeric bovine ATP synthase described here provide evidence of the operation of a Grotthus mechanism of proton translocation [40] in the inlet half channel of the transmembrane proton pathway through the membrane domain.
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