Proton half-channels and the a-subunit/c-ring mechanism of ATP synthase
Proton half-channels are two access paths in the membrane-embedded a-subunit of F-type ATP synthase. One path brings protons to the c-ring, and the other releases them after the ring has turned.15 Kühlbrandt describes the c-ring as a rotor driven by this proton flow.4 The arrangement matters because the torque of the ring is what drives ATP formation in the catalytic head.4
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- 2014, Trono D, Laus MN, Soccio M…
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- Rotational Mechanism of FO Motor in the…, 2022
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- 58 passages in 11 works
- Rewritten
- 2026-11-04
A model from alkaliphile work
Preiss and colleagues (2015) present a model of the F1Fo-ATP synthase built on work by other investigators. In it, protons pass through a half-channel of the a-subunit to an interface with the c-rotor ring.1 They cite Angevine and Fillingame (2003) and Dong and Fillingame (2010) for release into the bacterial cytoplasm through a second half-channel after a full rotation.1 In alkaliphilic Bacillus, residue K180 of helix 4 was identified as of interest. The authors say it was hypothesized to impede proton loss from the entry half-channel and so favour proton movement to the c-ring binding sites.2
Mutagenesis at high pH
The same review reports tests of that idea. In the earliest mutagenesis study, K180 was replaced by glycine, the consensus residue of non-alkaliphiles. Growth on malate at pH 10.5 fell sharply but not at pH 7.5, and ATP synthesis by loaded membrane vesicles fell sharply too. Replacing G212 by serine caused a much smaller defect.3 The review credits this study to Wang and colleagues (2004). It also mentions a later study that replaced K180 with several other residues.3
Mitochondrial structures
Kühlbrandt (2015) gives the rotor as 8 c-subunits in mammals and 10 in yeast.4 Spikes, Montgomery and Walker (2020) describe the bovine enzyme. Their inlet half-channel runs through two tilted helices of the a-subunit and delivers protons to cGlu-58 of the c-ring.5 In the outlet, they see density near aArg-159 that could be a bound water molecule, and they propose it accepts the proton leaving cGlu-58.6 Protasoni and Zeviani (2021) also give a conserved arginine of subunit a as favouring proton release on the matrix side, and they number it A210.8 The two numberings may or may not refer to the same residue.
Ring conformations and size
Kubo and Takada (2022) summarize work on the c-ring proton carriers. Simulations showed that the side chains change orientation depending on whether the residue faces the lipid or the a-subunit. Facing the a-subunit, the deprotonated side chain points outward and eases transfer to the half-channels.7 Didaran and colleagues (2026) note that ring size varies. Plant enzyme typically has about 14 c-subunits, giving about 4.67 protons per ATP. Tighter coupling raises the ATP yield per unit of proton motive force but can limit protective ΔpH formation unless counter-ion routes keep Δψ in check.9
The model indicates a path of protons through a “half-channel” of the membrane-embedded a-subunit, which leads to an interface that enables the proton to move from the a-subunit to the c-rotor ring
Preiss L, Hicks DB, Suzuki S, Meier T, Krulwich TA, 2015 · Alkaliphilic Bacteria with Impact on Industrial Applications, Concepts of Early… · open at passage 21Their hypothesized function was to act as an important impediment to proton loss from the entry half-channel of the a-subunit and thus promote successful movement of protons to the ion-binding sites of the c-ring.
Preiss L, Hicks DB, Suzuki S, Meier T, Krulwich TA, 2015 · Alkaliphilic Bacteria with Impact on Industrial Applications, Concepts of Early… · open at passage 23resulting in major loss of growth on malate at pH 10.5 but not 7.5 and major loss of ATP synthesis by ADP + Pi-loaded membrane vesicles while replacement of G212 by serine had a much smaller defect
Preiss L, Hicks DB, Suzuki S, Meier T, Krulwich TA, 2015 · Alkaliphilic Bacteria with Impact on Industrial Applications, Concepts of Early… · open at passage 23Protons moving through the Fo complex in the membrane drive a rotor ring composed of 8 (in mammals [35]) or 10 (in yeast [36]) c-subunits.
Kühlbrandt W, 2015 · Structure and function of mitochondrial membrane protein complexes · open at passage 15an inlet half-channel passing through α-helices aH5 and aH6 in the a-subunit tilted at 30° to the plane of the membrane provides ingress for protons to negatively charged Glu-58 residues in c-subunits
Spikes TE, Montgomery MG, Walker JE, 2020 · Structure of the dimeric ATP synthase from bovine mitochondria · open at passage 11strong density near aArg-159, with the hydroxyl moiety of aTyr-221 pointing toward it, could be a specifically bound water molecule
Spikes TE, Montgomery MG, Walker JE, 2020 · Structure of the dimeric ATP synthase from bovine mitochondria · open at passage 15the final dissociation of the proton at the matrix side favored by the positive charge on a conserved arginine residue (A210) of subunit a
Protasoni M, Zeviani M, 2021 · Mitochondrial Structure and Bioenergetics in Normal and Disease Conditions · open at passage 87when it faces the a-subunit, the deprotonated side chains face outward (deprotonated-extended conformation), facilitating proton transfer from the c-ring to the half-channels of the a-subunit
Kubo S, Takada S, 2022 · Rotational Mechanism of FO Motor in the F-Type ATP Synthase Driven by the… · open at passage 15Plant ATP synthase typically assembles a C-ring of ~14 subunits, so one full rotation returns ~14 protons and synthesizes ~3 ATP
Didaran F, MacPherson S, Cherestes A, Zohrabi S, Lefsrud M, 2026 · Proton motive force partitioning links energy and redox balance to… · open at passage 16