Structure and conformational states of the bovine mitochondrial ATP synthase by cryo-EM.

TitleStructure and conformational states of the bovine mitochondrial ATP synthase by cryo-EM.
Publication TypeJournal Article
Year of Publication2015
AuthorsZhou, A, Rohou, A, Schep, DG, Bason, JV, Montgomery, MG, Walker, JE, Grigorieff, N, Rubinstein, JL
Date Published2015 Oct 06
KeywordsAnimals, Cattle, Computational Biology, Cryoelectron Microscopy, Imaging, Three-Dimensional, Mitochondrial Proton-Translocating ATPases, Models, Molecular, Protein Conformation, Protein Folding

Adenosine triphosphate (ATP), the chemical energy currency of biology, is synthesized in eukaryotic cells primarily by the mitochondrial ATP synthase. ATP synthases operate by a rotary catalytic mechanism where proton translocation through the membrane-inserted FO region is coupled to ATP synthesis in the catalytic F1 region via rotation of a central rotor subcomplex. We report here single particle electron cryomicroscopy (cryo-EM) analysis of the bovine mitochondrial ATP synthase. Combining cryo-EM data with bioinformatic analysis allowed us to determine the fold of the a subunit, suggesting a proton translocation path through the FO region that involves both the a and b subunits. 3D classification of images revealed seven distinct states of the enzyme that show different modes of bending and twisting in the intact ATP synthase. Rotational fluctuations of the c8-ring within the FO region support a Brownian ratchet mechanism for proton-translocation-driven rotation in ATP synthases.

Alternate JournalElife
Citation Key10.7554/eLife.10180
PubMed ID26439008
PubMed Central IDPMC4718723
Grant ListMC_EX_MR/M009858/1 / / Medical Research Council / United Kingdom
MOP 81294 / / Canadian Institutes of Health Research / Canada
U105663150 / / Medical Research Council / United Kingdom