The First Extracellular Linker Is Important for Several Aspects of the Gating Mechanism of Human TRPA1 Channel

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F17%3A00473936" target="_blank" >RIV/67985823:_____/17:00473936 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11320/17:10370888

Výsledek na webu

<a href="http://dx.doi.org/10.3389/fnmol.2017.00016" target="_blank" >http://dx.doi.org/10.3389/fnmol.2017.00016</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3389/fnmol.2017.00016" target="_blank" >10.3389/fnmol.2017.00016</a>

Jazyk výsledku

angličtina

Název v původním jazyce

The First Extracellular Linker Is Important for Several Aspects of the Gating Mechanism of Human TRPA1 Channel

Popis výsledku v původním jazyce

Transient receptor potential ankyrin 1 (TRPA1) is an excitatory ion channel involved in pain, inflammation and itching. This channel gates in response to many irritant and proalgesic agents, and can be modulated by calcium and depolarizing voltage. While the closed-state structure of TRPA1 has been recently resolved, also having its open state is essential for understanding how this channel works. Here we use molecular dynamics simulations combined with electrophysiological measurements and systematic mutagenesis to predict and explore the conformational changes coupled to the expansion of the presumptive channel's lower gate. We show that, upon opening, the upper part of the sensor module approaches the pore domain of an adjacent subunit and the conformational dynamics of the first extracellular flexible loop may govern the voltage-dependence of multimodal gating, thereby serving to stabilize the open state of the channel. These results are generally important in understanding the structure and function of TRPA1 and offer new insights into the gating mechanism of TRPA1 and related channels.

Název v anglickém jazyce

The First Extracellular Linker Is Important for Several Aspects of the Gating Mechanism of Human TRPA1 Channel

Popis výsledku anglicky

Transient receptor potential ankyrin 1 (TRPA1) is an excitatory ion channel involved in pain, inflammation and itching. This channel gates in response to many irritant and proalgesic agents, and can be modulated by calcium and depolarizing voltage. While the closed-state structure of TRPA1 has been recently resolved, also having its open state is essential for understanding how this channel works. Here we use molecular dynamics simulations combined with electrophysiological measurements and systematic mutagenesis to predict and explore the conformational changes coupled to the expansion of the presumptive channel's lower gate. We show that, upon opening, the upper part of the sensor module approaches the pore domain of an adjacent subunit and the conformational dynamics of the first extracellular flexible loop may govern the voltage-dependence of multimodal gating, thereby serving to stabilize the open state of the channel. These results are generally important in understanding the structure and function of TRPA1 and offer new insights into the gating mechanism of TRPA1 and related channels.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30103 - Neurosciences (including psychophysiology)

Projekt

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

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2017

Kód důvěrnosti údajů

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

Název periodika

Frontiers in Molecular Neuroscience

ISSN

1662-5099

e-ISSN

—

Svazek periodika

10

Číslo periodika v rámci svazku

Jan 31

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

19

Strana od-do

—

Kód UT WoS článku

000392971600002

EID výsledku v databázi Scopus

2-s2.0-85014040711