Structural highlights
Function
[VATL2_YEAST] Proton-conducting pore forming subunit of the membrane integral V0 complex of vacuolar ATPase. V-ATPase is responsible for acidifying a variety of intracellular compartments in eukaryotic cells.[1] [2] [VA0D_YEAST] Vacuolar ATPase is responsible for acidifying a variety of intracellular compartments in eukaryotic cells. The active enzyme consists of a catalytic V1 domain attached to an integral membrane V0 proton pore complex. This subunit is a non-integral membrane component of the membrane pore domain and is required for proper assembly of the V0 sector. Might be involved in the regulated assembly of V1 subunits onto the membrane sector or alternatively may prevent the passage of protons through V0 pores. [VATO_YEAST] Proton-conducting pore forming subunit of the membrane integral V0 complex of vacuolar ATPase. V-ATPase is responsible for acidifying a variety of intracellular compartments in eukaryotic cells. [VATL1_YEAST] Proton-conducting pore forming subunit of the membrane integral V0 complex of vacuolar ATPase. V-ATPase is responsible for acidifying a variety of intracellular compartments in eukaryotic cells. It is an electrogenic proton pump that generates a proton motive force of 180 mv, inside positive and acidic, in the vacuolar membrane vesicles. [VA0E_YEAST] Subunit of the integral membrane V0 complex of vacuolar ATPase. V-ATPase is responsible for acidifying a variety of intracellular compartments in eukaryotic cells.[3]
Publication Abstract from PubMed
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 V1 region drives proton translocation through the membrane-embedded VO 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 V1 and VO regions of the V-ATPase by starving the yeast Saccharomyces cerevisiae, allowing us to obtain a ~3.9-A resolution electron cryomicroscopy map of the VO complex and build atomic models for the majority of its subunits. The analysis reveals the structures of subunits ac8c'cde 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.
Atomic model for the membrane-embedded VO motor of a eukaryotic V-ATPase.,Mazhab-Jafari MT, Rohou A, Schmidt C, Bueler SA, Benlekbir S, Robinson CV, Rubinstein JL Nature. 2016 Oct 24;539(7627):118-122. doi: 10.1038/nature19828. PMID:27776355[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Umemoto N, Ohya Y, Anraku Y. VMA11, a novel gene that encodes a putative proteolipid, is indispensable for expression of yeast vacuolar membrane H(+)-ATPase activity. J Biol Chem. 1991 Dec 25;266(36):24526-32. PMID:1837023
- ↑ Hirata R, Graham LA, Takatsuki A, Stevens TH, Anraku Y. VMA11 and VMA16 encode second and third proteolipid subunits of the Saccharomyces cerevisiae vacuolar membrane H+-ATPase. J Biol Chem. 1997 Feb 21;272(8):4795-803. PMID:9030535
- ↑ Davis-Kaplan SR, Ward DM, Shiflett SL, Kaplan J. Genome-wide analysis of iron-dependent growth reveals a novel yeast gene required for vacuolar acidification. J Biol Chem. 2004 Feb 6;279(6):4322-9. Epub 2003 Nov 21. PMID:14594803 doi:http://dx.doi.org/10.1074/jbc.M310680200
- ↑ Mazhab-Jafari MT, Rohou A, Schmidt C, Bueler SA, Benlekbir S, Robinson CV, Rubinstein JL. Atomic model for the membrane-embedded VO motor of a eukaryotic V-ATPase. Nature. 2016 Oct 24;539(7627):118-122. doi: 10.1038/nature19828. PMID:27776355 doi:http://dx.doi.org/10.1038/nature19828
