Calmodulin and S100A1 protein interact with N terminus of TRPM3 channel

J Biol Chem. 2012 May 11;287(20):16645-55. doi: 10.1074/jbc.M112.350686. Epub 2012 Mar 27.


Transient receptor potential melastatin 3 ion channel (TRPM3) belongs to the TRP family of cation-permeable ion channels involved in many important biological functions such as pain transduction, thermosensation, and mechanoregulation. The channel was reported to play an important role in Ca(2+) homeostasis, but its gating mechanisms, functions, and regulation are still under research. Utilizing biophysical and biochemical methods, we characterized two independent domains, Ala-35-Lys-124 and His-291-Gly-382, on the TRPM3 N terminus, responsible for interactions with the Ca(2+)-binding proteins calmodulin (CaM) and S100A1. We identified several positively charged residues within these domains as having a crucial impact on CaM/S100A1 binding. The data also suggest that the interaction is calcium-dependent. We also performed competition assays, which suggested that CaM and S100A1 are able to compete for the same binding sites within the TRPM3 N terminus. This is the first time that such an interaction has been shown for TRP family members.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution
  • Binding Sites
  • Calmodulin / chemistry
  • Calmodulin / genetics
  • Calmodulin / metabolism*
  • Humans
  • Mutation, Missense
  • Protein Binding
  • S100 Proteins / chemistry
  • S100 Proteins / genetics
  • S100 Proteins / metabolism*
  • TRPM Cation Channels / chemistry
  • TRPM Cation Channels / genetics
  • TRPM Cation Channels / metabolism*


  • Calmodulin
  • S100 Proteins
  • S100A1 protein
  • TRPM Cation Channels
  • TRPM3 protein, human