Article

Function, structure and regulation of the vacuolar (H+)-ATPases

Department of Physiology, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA.
Archives of Biochemistry and Biophysics (Impact Factor: 3.04). 09/2008; 476(1):33-42. DOI: 10.1016/j.abb.2008.03.025
Source: PubMed

ABSTRACT The vacuolar ATPases (or V-ATPases) are ATP-driven proton pumps that function to both acidify intracellular compartments and to transport protons across the plasma membrane. Intracellular V-ATPases function in such normal cellular processes as receptor-mediated endocytosis, intracellular membrane traffic, prohormone processing, protein degradation and neurotransmitter uptake, as well as in disease processes, including infection by influenza and other viruses and killing of cells by anthrax and diphtheria toxin. Plasma membrane V-ATPases are important in such physiological processes as urinary acidification, bone resorption and sperm maturation as well as in human diseases, including osteopetrosis, renal tubular acidosis and tumor metastasis. V-ATPases are large multi-subunit complexes composed of a peripheral domain (V(1)) responsible for hydrolysis of ATP and an integral domain (V(0)) that carries out proton transport. Proton transport is coupled to ATP hydrolysis by a rotary mechanism. V-ATPase activity is regulated in vivo using a number of mechanisms, including reversible dissociation of the V(1) and V(0) domains, changes in coupling efficiency of proton transport and ATP hydrolysis and changes in pump density through reversible fusion of V-ATPase containing vesicles. V-ATPases are emerging as potential drug targets in treating a number of human diseases including osteoporosis and cancer.

0 Followers
 · 
113 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The membrane domain of rotary ATPases (Fo/Vo/Ao) contains a membrane-embedded rotor ring which rotates against an adjacent cation channel-forming subunit during catalysis. The mechanism that allows stabilization of the highly mobile and yet tightly connected domains during operation while not impeding rotation is unknown. Remarkably, all known ATPase rotor rings are filled by lipids. In the crystal structure of the rotor ring of a V-ATPase from Enterococcus hirae the ring filling lipids form a proper membrane that is lower with respect to the embedding membrane surrounding both subunits. I propose first, that a vertical shift between lumenal lipids and embedding outside membrane is a general feature of rotor rings and second that it leads to a radial potential fall-off between rotor ring and cation channel, creating attractive forces that impact rotor-stator interaction in Fo/Vo/Ao during rotation.
    BIOPHYSICS 01/2011; 7:99-104. DOI:10.2142/biophysics.7.99
  • [Show abstract] [Hide abstract]
    ABSTRACT: Vacuolar type rotary H+-ATPases (VoV1) couple ATP synthesis/hydrolysis by V1 with proton translocation by Vo via rotation of a central rotor apparatus composed of the V1-DF rotor shaft, a socket-like Vo-C (eukaryotic Vo-d) and the hydrophobic rotor ring. Reconstitution experiments using subcomplexes revealed a weak binding affinity of V1-DF to Vo-C despite the fact that torque needs to be transmitted between V1-DF and Vo-C for the tight energy coupling between V1 and Vo. Mutation of a short helix at the tip of V1-DF caused intramolecular uncoupling of VoV1, suggesting that proper fitting of the short helix of V1-D into the socket of Vo-C is required for tight energy coupling between V1 and Vo. To account for the apparently contradictory properties of the interaction between V1-DF and Vo-C (weak binding affinity but strict requirement for torque transmission), we propose a model in which the relationship between V1-DF and Vo-C corresponds to that between a slotted screwdriver and a head of slotted screw. This model is consistent with our previous result in which the central rotor apparatus is not the major factor for the association of V1 with Vo (Kishikawa and Yokoyama, J Biol Chem. 2012 24597-24603).
    PLoS ONE 03/2015; 10(3):e0119602. DOI:10.1371/journal.pone.0119602 · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The vacuolar H(+)-ATPase (V-ATPase) has long been appreciated to function as an electrogenic H(+) pump. By altering the pH of intracellular compartments, the V-ATPase dictates enzyme activity, governs the dissociation of ligands from receptors and promotes the coupled transport of substrates across membranes, a role often aided by the generation of a transmembrane electrical potential. In tissues where the V-ATPase is expressed at the plasma membrane, it can serve to acidify the extracellular microenvironment. More recently, however, the V-ATPase has been implicated in a bewildering variety of additional roles that seem independent of its ability to translocate H(+). These non-canonical functions, which include fusogenicity, cytoskeletal tethering and metabolic sensing, are described in this Cell Science at a Glance article and accompanying poster, together with a brief overview of the conventional functions of the V-ATPase. © 2014. Published by The Company of Biologists Ltd.
    Journal of Cell Science 12/2014; 127(23):4987-93. DOI:10.1242/jcs.158550 · 5.33 Impact Factor

Full-text (2 Sources)

Download
60 Downloads
Available from
May 28, 2014