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


Type
Article
Change log
Authors
Zhou, Anna 
Rohou, Alexis 
Schep, Daniel G 
Bason, John V 
Montgomery, Martin G 
Abstract

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.

Description
Keywords
ATP synthase, biochemistry, biophysics, bovine, coevolution, cryo-EM, evolutionary covariance, structural biology, structure, Animals, Cattle, Computational Biology, Cryoelectron Microscopy, Imaging, Three-Dimensional, Mitochondrial Proton-Translocating ATPases, Models, Molecular, Protein Conformation, Protein Folding
Journal Title
Elife
Conference Name
Journal ISSN
2050-084X
2050-084X
Volume Title
4
Publisher
eLife Sciences Publications, Ltd
Sponsorship
Medical Research Council (MC_EX_MR/M009858/1)
Medical Research Council (MC_U105663150)