The characterization of a novel S100A1 binding site in the N-terminus of TRPM1
Language English Country Netherlands Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
27435061
DOI
10.1016/j.biocel.2016.07.014
PII: S1357-2725(16)30186-8
Knihovny.cz E-resources
- Keywords
- Binding site, Calcium-binding protein S100A1, Circular dichroism, Molecular modeling, Steady-state fluorescence anisotropy, TRPM1 channel,
- MeSH
- Hydrophobic and Hydrophilic Interactions MeSH
- TRPM Cation Channels chemistry metabolism MeSH
- Rats MeSH
- Humans MeSH
- Protein Domains MeSH
- S100 Proteins chemistry metabolism MeSH
- Protein Structure, Secondary MeSH
- Amino Acid Sequence MeSH
- Molecular Docking Simulation MeSH
- Calcium metabolism MeSH
- Protein Binding MeSH
- Binding Sites MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- TRPM Cation Channels MeSH
- S100 Proteins MeSH
- S100A1 protein MeSH Browser
- Trpm1 protein, rat MeSH Browser
- Calcium MeSH
Transient receptor potential melastatin-1 channel (TRPM1) is an important mediator of calcium influx into the cell that is expressed in melanoma and ON-bipolar cells. Similar to other members of the TRP channel family, the intracellular N- and C- terminal domains of TRPM1 are expected to play important roles in the modulation of TRPM1 receptor function. Among the most commonly occurring modulators of TRP channels are the cytoplasmically expressed calcium binding proteins calmodulin and S100 calcium-binding protein A1 (S100A1), but the interaction of TRPM1 with S100A1 has not been described yet. Here, using a combination of biophysical and bioinformatics methods, we have determined that the N-terminal L242-E344 region of TRPM1 is a S100A1 binding domain. We show that formation of the TRPM1/S100A1 complex is calcium-dependent. Moreover, our structural model of the complex explained data obtained from fluorescence spectroscopy measurements revealing that the complex formation is facilitated through interactions of clusters positively charged (K271A, R273A, R274A) and hydrophobic (L263A, V270A, L276A) residues at the N-terminus of TRPM1. Taken together, our data suggest a molecular mechanism for the potential regulation of TRPM1 by S100A1.
Institute of Biotechnology Czech Academy of Sciences BIOCEV 25250 Vestec Czech Republic
Institute of Physiology Czech Academy of Sciences 14220 Prague Czech Republic
References provided by Crossref.org
Interaction of Calmodulin with TRPM: An Initiator of Channel Modulation
TRPM7 N-terminal region forms complexes with calcium binding proteins CaM and S100A1
Mapping of CaM, S100A1 and PIP2-Binding Epitopes in the Intracellular N- and C-Termini of TRPM4
TRPM6 N-Terminal CaM- and S100A1-Binding Domains
