title: Calmodulin and S100A1 protein interact with N terminus of TRPM3 channel.
abstract: 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.
authors.affiliation: Institute of Physiology, Academy of Sciences of the Czech Republic, Videnska 1083, 142 20 Prague, Czech Republic.
authors.forename: Blanka
authors.initials: B
authors.lastname: Holakovska
authors.forename: Lenka
authors.initials: L
authors.lastname: Grycova
authors.forename: Michaela
authors.initials: M
authors.lastname: Jirku
authors.forename: Miroslav
authors.initials: M
authors.lastname: Sulc
authors.forename: Ladislav
authors.initials: L
authors.lastname: Bumba
authors.forename: Jan
authors.initials: J
authors.lastname: Teisinger
mesh_terms: D019943:Amino Acid Substitution; D001665:Binding Sites; D002147:Calmodulin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020125:Mutation, Missense; D011485:Protein Binding; D009418:S100 Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D050053:TRPM Cation Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D002147:Calmodulin; D009418:S100 Proteins; C110294:S100A1 protein; D050053:TRPM Cation Channels; C475667:TRPM3 protein, human