5TJ5

Atomic model for the membrane-embedded motor of a eukaryotic V-ATPase

Summary for 5TJ5

• Entry DOI: 10.2210/pdb5tj5/pdb
• EMDB information: 8409
• Descriptor: V-type proton ATPase subunit a, V-type proton ATPase subunit c'', V-type proton ATPase subunit c', ... (7 entities in total)
• Functional Keywords: rotary atpase, vacuolar-type atpase, electron cryomicroscopy, vo region, membrane protein, motor protein
• Biological source: Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast); More
• Total number of polymer chains: 14
• Total formula weight: 273563.44

Authors

Mazhab-Jafari, M.T.,Rohou, A.,Schmidt, C.,Bueler, S.A.,Benlekbir, S.,Robinson, C.V.,Rubinstein, J.L. (deposition date: 2016-10-03, release date: 2016-10-26, Last modification date: 2024-03-13)

Primary citation

Mazhab-Jafari, M.T.,Rohou, A.,Schmidt, C.,Bueler, S.A.,Benlekbir, S.,Robinson, C.V.,Rubinstein, J.L.
Atomic model for the membrane-embedded VO motor of a eukaryotic V-ATPase.
Nature, 539:118-122, 2016

PubMed Abstract: Vacuolar-type ATPases (V-ATPases) are ATP-powered proton pumps involved in processes such as endocytosis, lysosomal degradation, secondary transport, TOR signalling, and osteoclast and kidney function. ATP hydrolysis in the soluble catalytic V region drives proton translocation through the membrane-embedded V region via rotation of a rotor subcomplex. Variability in the structure of the intact enzyme has prevented construction of an atomic model for the membrane-embedded motor of any rotary ATPase. We induced dissociation and auto-inhibition of the V and V regions of the V-ATPase by starving the yeast Saccharomyces cerevisiae, allowing us to obtain a ~3.9-Å resolution electron cryomicroscopy map of the V complex and build atomic models for the majority of its subunits. The analysis reveals the structures of subunits acc'c″de and a protein that we identify and propose to be a new subunit (subunit f). A large cavity between subunit a and the c-ring creates a cytoplasmic half-channel for protons. The c-ring has an asymmetric distribution of proton-carrying Glu residues, with the Glu residue of subunit c″ interacting with Arg735 of subunit a. The structure suggests sequential protonation and deprotonation of the c-ring, with ATP-hydrolysis-driven rotation causing protonation of a Glu residue at the cytoplasmic half-channel and subsequent deprotonation of a Glu residue at a luminal half-channel.

PubMed: 27776355
DOI: 10.1038/nature19828

Experimental method

ELECTRON MICROSCOPY (3.9 Å)