The TRPV5/6 calcium channels contain multiple calmodulin binding sites with differential binding properties

J Struct Funct Genomics. 2012 Jun;13(2):91-100. doi: 10.1007/s10969-012-9128-4. Epub 2012 Feb 22.


The epithelial Ca(2+) channels TRPV5/6 (transient receptor potential vanilloid 5/6) are thoroughly regulated in order to fine-tune the amount of Ca(2+) reabsorption. Calmodulin has been shown to be involved into calcium-dependent inactivation of TRPV5/6 channels by binding directly to the distal C-terminal fragment of the channels (de Groot et al. in Mol Cell Biol 31:2845-2853, 12). Here, we investigate this binding in detail and find significant differences between TRPV5 and TRPV6. We also identify and characterize in vitro four other CaM binding fragments of TRPV5/6, which likely are also involved in TRPV5/6 channel regulation. The five CaM binding sites display diversity in binding modes, binding stoichiometries and binding affinities, which may fine-tune the response of the channels to varying Ca(2+)-concentrations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Calcium / chemistry
  • Calcium Channels / chemistry*
  • Calmodulin / chemistry*
  • Cell Membrane / chemistry
  • Escherichia coli / chemistry
  • Escherichia coli / genetics
  • Humans
  • Magnetic Resonance Spectroscopy
  • Molecular Sequence Data
  • Peptide Fragments / chemistry
  • Peptide Fragments / isolation & purification
  • Protein Binding
  • Protein Interaction Mapping
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / isolation & purification
  • TRPV Cation Channels / chemistry*
  • Thermodynamics
  • Tryptophan / chemistry
  • Xenopus laevis / genetics


  • Calcium Channels
  • Calmodulin
  • Peptide Fragments
  • Recombinant Proteins
  • TRPV Cation Channels
  • TRPV5 protein, human
  • TRPV6 protein, human
  • Tryptophan
  • Calcium