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Annual Review of Biochemistry

Volume 88, 2019

Structure and Mechanisms of F-Type ATP Synthases

Abstract

FF ATP synthases produce most of the ATP in the cell. F-type ATP synthases have been investigated for more than 50 years, but a full understanding of their molecular mechanisms has become possible only with the recent structures of complete, functionally competent complexes determined by electron cryo-microscopy (cryo-EM). High-resolution cryo-EM structures offer a wealth of unexpected new insights. The catalytic F head rotates with the central -subunit for the first part of each ATP-generating power stroke. Joint rotation is enabled by subunit acting as a flexible hinge between F and the peripheral stalk. Subunit conducts protons to and from the -ring rotor through two conserved aqueous channels. The channels are separated by ∼6 Å in the hydrophobic core of F, resulting in a strong local field that generates torque to drive rotary catalysis in F. The structure of the chloroplast FF complex explains how ATPase activity is turned off at night by a redox switch. Structures of mitochondrial ATP synthase dimers indicate how they shape the inner membrane cristae. The new cryo-EM structures complete our picture of the ATP synthases and reveal the unique mechanism by which they transform an electrochemical membrane potential into biologically useful chemical energy.

Keyword(s): ATP synthase dimers, chloroplasts, cryo-EM, electron cryo-microscopy, membrane protein structure, mitochondria, proton channels, proton-motive force
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2019-06-20
2025-04-30
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Structure and Mechanisms of F-Type ATP Synthases
Annual Review of Biochemistry 88, 515 (2019); https://doi.org/10.1146/annurev-biochem-013118-110903
/content/journals/10.1146/annurev-biochem-013118-110903
/content/journals/10.1146/annurev-biochem-013118-110903
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Supplementary Data

  • Supplemental Video 1: ATP synthase dimer rows in mitochondrial cristae. Electron cryo-tomography of a whole small mitochondrion reveals rows of F1-Fo ATP synthase dimers (yellow arrowheads) along highly curved cristae ridges. Gray, outer membrane; blue, cristae membranes; transparent blue, inner boundary membrane; yellow, ATP synthase. Adapted from reference 60.

    Supplemental Video 2: Flexible coupling of c-ring rotor and F1 head. A morph of the 13 resolved rotary substates in the 2.7 Å cryo-EM structure of the Polytomella ATP synthase (81) indicates that the c-ring (yellow) rotates together with the central stalk (blue, subunit γ; cyan, subunit δ; pale blue, subunit ε) against subunit a (mid-blue) in three roughly equal ~120° steps. The F1 head moves with the central stalk for the first 20 to 30° of each step. Dark green, subunit α; light green, subunit β. The two-domain OSCP subunit (orange) works as a hinge between the moving F1 head and the stationary peripheral stalk (gray). Adapted from reference 81.

    Supplemental Video 3: Joint rotation of F1 head and central stalk. A section through the F1 head in Supplemental Video 2 at the level of the nucleotide binding sites shows that subunit γ (blue) engages with the catch loop (purple) of subunit β (light green), taking the F1 head with it for the first 20 to 30° of each rotary step, before it relaxes to the beginning of the next rotary step. Red, catalytic sites of the three β-subunits; yellow, binding sites of the structural ATP molecules in the three α-subunits (dark green). Gray, peripheral stalk. Adapted from reference 81.

    Supplemental Video 4: The δ/OSCP hinge. The N-terminal α-helical domain of the two-domain subunit δ/OSCP (shown here is subunit OSCP of Polytomella mitochondrial ATP synthase) is attached to the F1 head by the N-terminal extensions of two of the three α-subunits (dark green). The C-terminal δ/OSCP domain is attached to the peripheral stalk (gray) by interaction of one OSCP helix with the N-terminal extension of the third α-subunit. Joint rotation of the F1 head with the central stalk for the first part of each ATP-generating power stroke (see Supplemental Video 3) is facilitated by the single-peptide link which connects the two δ/OSCP domains, acting as a hinge. The hinge movement enables flexible coupling of the central rotor and F1 head and overcomes the symmetry mismatch between the near-threefold F1 head and the eight to 17-fold symmetry (tenfold for Polytomella or yeasts; 14-fold for chloroplasts; see Figure 9 and Supplemental Video 5) of the c-ring rotor. Adapted from reference 81.

    Supplemental Video 5: Proton translocation drives c-ring rotation. Protons entering from the chloroplast or cristae lumen through the access channel (transparent red) in subunit a (see Figure 11) protonate the negatively charged c-ring glutamate (stick representation; cGlu61 in chloroplast ATP synthase; cGlu111 in Polytomella mitochondria) in the middle of the membrane, as shown here for the chloroplast c14 ring. The protonated, uncharged glutamate partitions into the hydrophobic phase of the lipid bilayer. After rotation by n-1 subunits (where n is the number of c-subunits in the ring—14 in chloroplasts; 10 in Polytomella or yeast mitochondria; 8 in mammalian mitochondria), the protonated glutamate encounters the hydrophilic exit channel (transparent blue) in subunit a and the proton escapes to the ~pH 8 environment of the chloroplast stroma or mitochondrial matrix. A strictly conserved, positively charged arginine (aArg189 in chloroplasts; aArg239 in Polytomella mitochondria) separates the two channels. The ~6 Å edge-to-edge distance between the proton access and exit channels generates a strong local electrostatic field. The field acts on the deprotonated, negatively charged glutamate and facilitates directional c-ring rotation. Adapted from reference 48.

    Supplemental Video 6: Mitochondrial ATP synthase dimers reconstituted into liposomes. Electron cryo-tomography (cryo-ET) of lipid-reconstituted ATP synthase dimers (yellow) from the yeast Yarrowia lipolytica. The V-shaped dimers insert into preformed liposomes of E. coli polar lipid upon detergent removal. Dimers spontaneously associate into rows that shape the lipid bilayer (light blue) into ridges. The irregular spacing of dimers along a ridge indicates the absence of specific protein-protein interactions, which are therefore not required for row formation. Bi-directional insertion (which does not occur in vivo) converts the planar bilayer into a corrugated sheet. Adapted from reference 68.

    Note: Supplemental Videos and captions updated on May 16, 2019.

  • Article Type: Review Article

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