PIP2 and PIP3 interact with N-terminus region of TRPM4 channel
Jazyk angličtina Země Nizozemsko Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
26071843
DOI
10.1016/j.bpc.2015.06.004
PII: S0301-4622(15)30008-9
Knihovny.cz E-zdroje
- Klíčová slova
- Binding site, Circular dichroism, Molecular modeling, PIP2, Surface plasmon resonance, TRPM4 channel,
- MeSH
- dimyristoylfosfatidylcholin analogy a deriváty metabolismus MeSH
- fosfatidylinositol-4,5-difosfát metabolismus MeSH
- kationtové kanály TRPM chemie metabolismus MeSH
- lidé MeSH
- molekulární sekvence - údaje MeSH
- peptidové fragmenty chemie metabolismus MeSH
- sekundární struktura proteinů MeSH
- sekvence aminokyselin MeSH
- simulace molekulového dockingu MeSH
- vazba proteinů MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- 1,2-dimyristoyl-sn-glycero-3-ethylphosphocholine MeSH Prohlížeč
- dimyristoylfosfatidylcholin MeSH
- fosfatidylinositol-4,5-difosfát MeSH
- kationtové kanály TRPM MeSH
- peptidové fragmenty MeSH
- TRPM4 protein, human MeSH Prohlížeč
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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