title: PtdIns(4,5)P2 interacts with CaM binding domains on TRPM3 N-terminus.
abstract: TRPM3 has been reported to play an important role in Ca(2+) homeostasis, but its gating mechanisms and regulation via Ca(2+) are unknown. Ca(2+) binding proteins such as calmodulin (CaM) could be probable modulators of this ion channel. We have shown that this protein binds to two independent domains, A35-K124 and H291-G382 on the TRPM3 N-terminus, which contain conserved hydrophobic as well as positively charged residues in specific positions, and that these residues have a crucial impact on its binding. We also showed that the other Ca(2+) binding protein, S100A1, is able to bind to these regions and that CaM and S100A1 compete for these binding sites on the TRPM3 N-terminus. Moreover, our results suggest that another very important TRP channel activity modulator, PtdIns(4,5)P(2), interacts with the CaM/S100A1 binding sites on the TRPM3 N-terminus with high affinity.
authors.affiliation: Department of Protein Structures, Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic. holakov@biomed.cas.cz
authors.forename: Blanka
authors.initials: B
authors.lastname: Holendova
authors.forename: Lenka
authors.initials: L
authors.lastname: Grycova
authors.forename: Michaela
authors.initials: M
authors.lastname: Jirku
authors.forename: Jan
authors.initials: J
authors.lastname: Teisinger
mesh_terms: D001665:Binding Sites; D002147:Calmodulin / Q000378:metabolism*; D005454:Fluorescence Polarization; D008081:Liposomes / Q000378:metabolism; D008958:Models, Molecular; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D009418:S100 Proteins / Q000378:metabolism; D020349:Surface Plasmon Resonance; D050053:TRPM Cation Channels / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D002147:Calmodulin; D008081:Liposomes; D019269:Phosphatidylinositol 4,5-Diphosphate; D009418:S100 Proteins; C110294:S100A1 protein; D050053:TRPM Cation Channels