PIP2 and PIP3 interact with N-terminus region of TRPM4 channel

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F15%3A10296261" target="_blank" >RIV/00216208:11310/15:10296261 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/67985823:_____/15:00446449 RIV/61388971:_____/15:00446449 RIV/61388963:_____/15:00446449 RIV/00216208:11130/15:10296261 RIV/00216208:11120/15:43909877

Výsledek na webu

<a href="http://dx.doi.org/10.1016/j.bpc.2015.06.004" target="_blank" >http://dx.doi.org/10.1016/j.bpc.2015.06.004</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.bpc.2015.06.004" target="_blank" >10.1016/j.bpc.2015.06.004</a>

Jazyk výsledku

angličtina

Název v původním jazyce

PIP2 and PIP3 interact with N-terminus region of TRPM4 channel

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

PIP2 and PIP3 interact with N-terminus region of TRPM4 channel

Popis výsledku anglicky

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.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

CE - Biochemie

OECD FORD obor

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Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

S - Specificky vyzkum na vysokych skolach

Rok uplatnění

2015

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Biophysical Chemistry

ISSN

0301-4622

e-ISSN

—

Svazek periodika

205

Číslo periodika v rámci svazku

October

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

9

Strana od-do

24-32

Kód UT WoS článku

000358806500004

EID výsledku v databázi Scopus

2-s2.0-84930656138