Atomic model for the dimeric F _O region of mitochondrial ATP synthase

Abstract

Mitochondrial adenosine triphosphate (ATP) synthase produces the majority of ATP in eukaryotic cells, and its dimerization is necessary to create the inner membrane folds, or cristae, characteristic of mitochondria. Proton translocation through the membrane-embedded F region turns the rotor that drives ATP synthesis in the soluble F region. Although crystal structures of the F region have illustrated how this rotation leads to ATP synthesis, understanding how proton translocation produces the rotation has been impeded by the lack of an experimental atomic model for the F region. Using cryo-electron microscopy, we determined the structure of the dimeric F complex from at a resolution of 3.6 angstroms. The structure clarifies how the protons travel through the complex, how the complex dimerizes, and how the dimers bend the membrane to produce cristae.

High-resolution cryo-EM analysis of the yeast ATP synthase in a lipid membrane

“…Figure 4 and Movie 3 show the putative” half-channels” from the cytoplasm and to the matrix. Their location and identification is consistent with recent reports (11, 19–21). The matrix side half-channel is most obvious at the a/c interface, where the side chains of a number of residues appear to form a hydrophilic cavity that extends from c 1 Glu59 to the surface of the membrane phase (Fig.…”

“…It has been proposed that Arg176 prevents the short circuiting of protons in the proton pathway (18) as well as acting as a positive pole for attraction of the charged Glu59 (14). In the isolated F o structure (11) (which we are assigning as the “ground state” structure), atoms in the corresponding side chains of Arg176 and the closest Glu59 (c 2 Glu59) are separated by 5–7.5 Å, while in this structure, the side-chains move closer to within 3.8 Å (Fig. 3D).…”

High-Conductance Channel Formation in Yeast Mitochondria is Mediated by F-ATP Synthase e and g Subunits

“…Major species differences in F-ATP synthase primary structure are found in subunits e and g, which closely associate with the b subunit in a distinct lateral domain [10]. Although we cannot exclude that additional subunits may participate, our data suggest that these lateral domains could be the sites of Ca 2+ -dependent channel formation.…”

“…Consistently, genetic ablation of yeast subunits e and g causes desensitization of the pore to Ca 2+ with increased resistance to opening [4,18], yet whether these subunits directly contribute to channel formation remains unknown. Together with the first transmembrane (TM) a-helix of subunit b, subunits e and g are located in a lateral domain close to the interface between monomers formed by adjacent subunits a [10]. Here, we investigate whether this domain contributes to generation of the PTP/MMC.…”

Interplay between the electrostatic membrane potential and conformational changes in membrane proteins

“…), including those from the MFS family, multidrug and toxin extrusion (MATE) family, small multidrug resistance (SMR) family, and resistance nodulation‐cell division (RND)/AcrB family . Moreover, as an example of multi‐states MPs, the PMF‐driven, F 1 –F O type of ATP synthase possesses two half‐channels connecting to opposite sides of the membrane . Because of the special configuration of the focused electric field between the two half‐channels located within the stator (with force lines more‐or‐less parallel to the membrane plane), the protonatible rotor is driven to rotate continuously within the membrane plane (with the rotation axis parallel to the membrane normal), converting TM electrostatic potential of protons into mechanical energy of the rotor …”