Shared CaM- and S100A1-binding epitopes in the distal TRPM4 N terminus
Language English Country England, Great Britain Media print-electronic
Document type Comparative Study, Journal Article, Research Support, Non-U.S. Gov't
PubMed
29240297
DOI
10.1111/febs.14362
Knihovny.cz E-resources
- Keywords
- S100A1, TRPM4 channel, calmodulin, fluorescence anisotropy, ligand-binding domains,
- MeSH
- Databases, Protein MeSH
- Epitopes MeSH
- Expert Systems MeSH
- Fluorescence Polarization MeSH
- Protein Interaction Domains and Motifs MeSH
- Calmodulin chemistry genetics metabolism MeSH
- TRPM Cation Channels chemistry genetics metabolism MeSH
- Kinetics MeSH
- Protein Conformation MeSH
- Conserved Sequence MeSH
- Humans MeSH
- Ligands MeSH
- Models, Molecular * MeSH
- Mutation MeSH
- Peptide Fragments chemical synthesis chemistry genetics metabolism MeSH
- S100 Proteins chemistry genetics metabolism MeSH
- Recombinant Proteins chemistry metabolism MeSH
- Amino Acid Sequence MeSH
- Molecular Docking Simulation MeSH
- Amino Acid Substitution MeSH
- Binding Sites MeSH
- Computational Biology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
- Names of Substances
- CALM1 protein, human MeSH Browser
- Epitopes MeSH
- Calmodulin MeSH
- TRPM Cation Channels MeSH
- Ligands MeSH
- Peptide Fragments MeSH
- S100 Proteins MeSH
- Recombinant Proteins MeSH
- S100A1 protein MeSH Browser
- TRPM4 protein, human MeSH Browser
The transient receptor potential channel of melastatin 4 (TRPM4) belongs to a group of large ion receptors that are involved in countless cell signalling cascades. This unique member is ubiquitously expressed in many human tissues, especially in cardiomyocytes, where it plays an important role in cardiovascular processes. Transient receptor potential channels (TRPs) are usually constituted by intracellular N- and C- termini, which serve as mediators affecting allosteric modulation of channels, resulting in the regulation of the channel function. The TRPs tails contain a number of conserved epitopes that specifically bind the intracellular modulators. Here, we identify new binding sites for the calmodulin (CaM) and S100 calcium-binding protein A1 (S100A1), located in the very distal part of the TRPM4 N terminus. We have used chemically synthesized peptides of the TRPM4, mimicking the binding epitopes, along with fluorescence methods to determine and specify CaM- and S100A1-binding sites. We have found that the ligands binding epitopes at the TRPM4 N terminus overlap, but the interacting mechanism of both complexes is probably different. The molecular models supported by data from the fluorescence method confirmed that the complexes formations are mediated by the positively charged (R139, R140, R144) and hydrophobic (L134, L138, V143) residues present at the TRPM4 N terminus-binding epitopes. The data suggest that the molecular complexes of TRPM4/CaM and TRPM4/S100A1 would lead to the modulation of the channel functions.
Faculty of Mathematics and Physics Charles University Prague Czech Republic
Institute of Organic Chemistry and Biochemistry Czech Academy of Sciences Prague Czech Republic
Institute of Physiology Czech Academy of Sciences Prague Czech Republic
References provided by Crossref.org
Oligomerization Function of the Native Exon 5 Sequence of Ameloblastin Fused with Calmodulin
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
PDB
2K2F
