Transient receptor potential (TRP) channels are a wide family of non-selective ion channels responsible for monovalent and divalent cation influx into the cells. Members of this family are involved in many sensory processes such as invertebrate vision and hearing, mammalian temperature-, mechano- and chemo-sensation. The TRP channels discovered so far can be divided into seven subfamilies according to their primary structure: TRPV, TRPC, TRPA, TRPM, TRPP, TRPML and TRPN. All are predicted to have six transmembrane helices (S1–S6) and a pore-forming loop between S5 and S6, with varying sizes of intracellular amino and carboxy termini, and are thought to form tetrameric assemblies. Both the N- and C-terminal intracellular domains are comprised of many different domains that are responsible for binding different compounds that can regulate the channels. Our goal is to provide the structural insight into the interactions of TRP channels with ATP, calmodulin and PIP.

Results

We identified several positively charged residues within N- and C- terminal 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. 

Computer homology models of TRPM3 41–70 (A) and TRPM3 302–324 (B) with Ca²⁺-CaM (Holakovska et al., 2012).