Structural identification of cation binding pockets in the plasma membrane proton pump

Proc Natl Acad Sci U S A. 2010 Dec 14;107(50):21400-5. doi: 10.1073/pnas.1010416107. Epub 2010 Nov 22.


The activity of P-type plasma membrane H(+)-ATPases is modulated by H(+) and cations, with K(+) and Ca(2+) being of physiological relevance. Using X-ray crystallography, we have located the binding site for Rb(+) as a K(+) congener, and for Tb(3+) and Ho(3+) as Ca(2+) congeners. Rb(+) is found coordinated by a conserved aspartate residue in the phosphorylation domain. A single Tb(3+) ion is identified positioned in the nucleotide-binding domain in close vicinity to the bound nucleotide. Ho(3+) ions are coordinated at two distinct sites within the H(+)-ATPase: One site is at the interface of the nucleotide-binding and phosphorylation domains, and the other is in the transmembrane domain toward the extracellular side. The identified binding sites are suggested to represent binding pockets for regulatory cations and a H(+) binding site for protons leaving the pump molecule. This implicates Ho(3+) as a novel chemical tool for identification of proton binding sites.

MeSH terms

  • Binding Sites
  • Cations / chemistry*
  • Cell Membrane / chemistry*
  • Crystallography, X-Ray
  • Genetic Complementation Test
  • Metals / chemistry
  • Molecular Sequence Data
  • Point Mutation
  • Protein Structure, Tertiary*
  • Proton Pumps / chemistry*
  • Proton Pumps / genetics
  • Protons*
  • Saccharomyces cerevisiae


  • Cations
  • Metals
  • Proton Pumps
  • Protons