![]() Subsequent structures of F-type ( Guo et al., 2017 Hahn et al., 2016 Morales-Rios et al., 2015) and V-type ATPases ( Mazhab-Jafari et al., 2016) at 3.7 to 7 Å resolution have shown that the long membrane-intrinsic helix hairpins are a conserved and apparently essential feature of all rotary ATPases ( Kühlbrandt and Davies, 2016), but the reason for this was not understood until now. The longest helix bends around the c-ring, positioning the strictly conserved aArg239 and other key subunit a residues next to the c-subunit protonation site. The helix hairpins run roughly at right angles to the c-ring helices. The previous 6.2 Å cryo-EM map of the Polytomella ATP synthase dimer indicated two long, membrane-intrinsic helix hairpins in subunit a ( Allegretti et al., 2015), but did not resolve sidechains. A conserved glutamate ( cGlu111 in Polytomella) serves as the c-subunit proton-binding site ( Meier et al., 2005 Pogoryelov et al., 2009). Mammalian mitochondria have a c 8-ring, while yeasts ( Hahn et al., 2016 Stock et al., 1999) and Polytomella ( Allegretti et al., 2015) have 10 c-ring subunits, which we refer to as cA to cJ. Rotor rings of F-type ATP synthases consist of 8 ( Watt et al., 2010 Zhou et al., 2015) to 15 ( Pogoryelov et al., 2009) identical c-subunits that each form a hydrophobic helix hairpin. Protonation and deprotonation of these glutamates drives ring rotation and ATP synthesis. 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. We have determined the structure of the complete mitochondrial ATP synthase dimer from the unicellular green alga Polytomella sp. The recent cryo-EM structure of the F o subcomplex dimer isolated from yeast mitochondria ( Guo et al., 2017) indicated the positions of key residues in the proton pathway. Until now, no high-resolution structure of an intact, functionally competent mitochondrial ATP synthase has been reported. Understanding how this fundamental process generates rotary force requires an atomic model of the proton pathway. Rotation is driven by protons flowing down the membrane gradient through the F o subcomplex. ATP synthases consist of the catalytic F 1 head and the F o subcomplex in the membrane ( von Ballmoos et al., 2009). The F0 subunit would be the portion of the complex that's embedded in the membrane, and the F1 component would be the part that is sticking out into the matrix.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). Another way of describing this complex is calling it the F0 and F1 subunits, you'll see that terminology as well. And then they come out of that channel into the matrix, and that's how the protons get back into the matrix. And that's where the protons go - they go in through that channel, then they move from one channel to the other and when they move, they drive the c ring to rotate. If you take a close look at the "a" purple unit up at the top, looks like a half moon, you can see two channels in it that go from the outside of the matrix to the inside of the matrix. The purple alpha a, b2, and delta parts on the left are very important because they basically hold the alpha and beta subunits in place so that when the c ring spins it won't just spin the whole thing, it actually spins relative to the rest of it. And it's got a long arm that stretches into the alpha-beta complex - and then when it rotates, it kind of nudges the alpha and beta subunits into various configurations which make the ATP get synthesized out of ADP and phosphate. And you see how that c ring would rotate? It rotates that gamma subunit down there in the middle (that's the red one). ![]() The other part, which consists of the purple part on the left - the a, b2, delta, and then also the orange and yellow parts on the bottom, the alpha and beta - all of that is a separate unit which more or less stays in place. ![]() Those all rotate - and the rotation of those is driven by the protons, the proton-motive force. ![]() There is the c ring and the gamma and epsilon units, that you see (the red and the green units attached to the blue c ring there).
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