The V-type H+ ATPase: molecular structure and function, physiological roles and regulation

Department of Biomedical Sciences, Cornell University, Итак, New York, United States
Journal of Experimental Biology (Impact Factor: 3). 03/2006; 209(Pt 4):577-89. DOI: 10.1242/jeb.02014
Source: PubMed

ABSTRACT It was nearly 30 years before the V-type H+ ATPase was admitted to the small circle of bona fide transport ATPases alongside F-type and P-type ATPases. The V-type H+ ATPase is an ATP-driven enzyme that transforms the energy of ATP hydrolysis to electrochemical potential differences of protons across diverse biological membranes via the primary active transport of H+. In turn, the transmembrane electrochemical potential of H+ is used to drive a variety of (i) secondary active transport systems via H+-dependent symporters and antiporters and (ii) channel-mediated transport systems. For example, expression of Cl- channels or transporters next to the V-type H+ ATPase in vacuoles of plants and fungi and in lysosomes of animals brings about the acidification of the endosomal compartment, and the expression of the H+/neurotransmitter antiporter next to the V-type H+ ATPase concentrates neurotransmitters in synaptic vesicles. First found in association with endosomal membranes, the V-type H+ ATPase is now also found in increasing examples of plasma membranes where the proton pump energizes transport across cell membranes and entire epithelia. The molecular details reveal up to 14 protein subunits arranged in (i) a cytoplasmic V1 complex, which mediates the hydrolysis of ATP, and (ii) a membrane-embedded V0 complex, which translocates H+ across the membrane. Clever experiments have revealed the V-type H+ ATPase as a molecular motor akin to F-type ATPases. The hydrolysis of ATP turns a rotor consisting largely of one copy of subunits D and F of the V1 complex and a ring of six or more copies of subunit c of the V0 complex. The rotation of the ring is thought to deliver H+ from the cytoplasmic to the endosomal or extracellular side of the membrane, probably via channels formed by subunit a. The reversible dissociation of V1 and V0 complexes is one mechanism of physiological regulation that appears to be widely conserved from yeast to animal cells. Other mechanisms, such as subunit-subunit interactions or interactions of the V-type H+ ATPase with other proteins that serve physiological regulation, remain to be explored. Some diseases can now be attributed to genetic alterations of specific subunits of the V-type H+ ATPase.

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Available from: Helmut Wieczorek, Mar 28, 2014
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    • "Vacuolar-type H+-ATPase (V-ATPase)-driven proton pumping and organellar acidification are essential for vesicular trafficking in both the exocytotic and endocytotic pathways in eukaryotic cells. This protein is an ATPdriven enzyme that transforms the energy from ATP hydrolysis to electrochemical potential differences of protons across many kinds biological membranes by actively transporting H + (Beyenbach and Wieczorek, 2006; Marshansky and Futai, 2008). Although V-ATPase has initial been identified initially in endosomal membranes, it is also found in plasma membranes where the proton pump supports molecular transport across cell membranes and the entire epithelia. "
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