Structure and function of the vacuolar H+-ATPase: moving from low-resolution models to high-resolution structures

J Bioenerg Biomembr. 2003 Aug;35(4):337-45. doi: 10.1023/a:1025728915565.


In the absence of a high-resolution structure for the vacuolar H+-ATPase, a number of approaches can yield valuable information about structure/function relationships in the enzyme. Electron microscopy can provide not only a representation of the overall architecture of the complex, but also a low-resolution map onto which structures solved for individually expressed subunits can be fitted. Here we review the possibilities for electron microscopy of the Saccharomyces V-ATPase and examine the suitability of V-ATPase subunits for expression in high yield prokaryotic systems, a key step towards high-resolution structural studies. We also review the role of experimentally-derived structural models in understanding structure/function relationships in the V-ATPase, with particular reference to the complex of proton-translocating 16 kDa proteolipids in the membrane domain of the V-ATPase. This model in turn makes testable predictions about the sites of binding of bafilomycins and the functional interactions between the proteolipid and the single-copy membrane subunit Vph1p, with implications for the constitution of the proton translocation pathway.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cell Membrane / chemistry
  • Models, Molecular
  • Molecular Structure
  • Solubility
  • Vacuolar Proton-Translocating ATPases / chemistry*
  • Vacuolar Proton-Translocating ATPases / physiology*


  • Vacuolar Proton-Translocating ATPases