PIP2 and PIP3 interact with N-terminus region of TRPM4 channel
Language English Country Netherlands Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
26071843
DOI
10.1016/j.bpc.2015.06.004
PII: S0301-4622(15)30008-9
Knihovny.cz E-resources
- Keywords
- Binding site, Circular dichroism, Molecular modeling, PIP2, Surface plasmon resonance, TRPM4 channel,
- MeSH
- Dimyristoylphosphatidylcholine analogs & derivatives metabolism MeSH
- Phosphatidylinositol 4,5-Diphosphate metabolism MeSH
- TRPM Cation Channels chemistry metabolism MeSH
- Humans MeSH
- Molecular Sequence Data MeSH
- Peptide Fragments chemistry metabolism MeSH
- Protein Structure, Secondary MeSH
- Amino Acid Sequence MeSH
- Molecular Docking Simulation MeSH
- Protein Binding MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- 1,2-dimyristoyl-sn-glycero-3-ethylphosphocholine MeSH Browser
- Dimyristoylphosphatidylcholine MeSH
- Phosphatidylinositol 4,5-Diphosphate MeSH
- TRPM Cation Channels MeSH
- Peptide Fragments MeSH
- TRPM4 protein, human MeSH Browser
The transient receptor potential melastatin 4 (TRPM4) is a calcium-activated non-selective ion channel broadly expressed in a variety of tissues. Receptor has been identified as a crucial modulator of numerous calcium dependent mechanisms in the cell such as immune response, cardiac conduction, neurotransmission and insulin secretion. It is known that phosphoinositide lipids (PIPs) play a unique role in the regulation of TRP channel function. However the molecular mechanism of this process is still unknown. We characterized the binding site of PIP2 and its structural analogue PIP3 in the E733-W772 proximal region of the TRPM4 N-terminus via biophysical and molecular modeling methods. The specific positions R755 and R767 in this domain were identified as being important for interactions with PIP2/PIP3 ligands. Their mutations caused a partial loss of PIP2/PIP3 binding specificity. The interaction of PIP3 with TRPM4 channels has never been described before. These findings provide new insight into the ligand binding domains of the TRPM4 channel.
3rd Faculty of Medicine Charles University Prague 10000 Prague Czech Republic
Institute of Microbiology Academy of Sciences of the Czech Republic 14220 Prague Czech Republic
Institute of Physiology Academy of Sciences of the Czech Republic 14220 Prague Czech Republic
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