Structural mechanism of heat-induced opening of a temperature-sensitive TRP channel

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F21%3A00544567" target="_blank" >RIV/67985823:_____/21:00544567 - isvavai.cz</a>

Výsledek na webu

<a href="https://doi.org/10.1038/s41594-021-00615-4" target="_blank" >https://doi.org/10.1038/s41594-021-00615-4</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41594-021-00615-4" target="_blank" >10.1038/s41594-021-00615-4</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Structural mechanism of heat-induced opening of a temperature-sensitive TRP channel

Popis výsledku v původním jazyce

Numerous physiological functions rely on distinguishing temperature through temperature-sensitive transient receptor potential channels (thermo-TRPs). Although the function of thermo-TRPs has been studied extensively, structural determination of their heat- and cold-activated states has remained a challenge. Here, we present cryo-EM structures of the nanodisc-reconstituted wild-type mouse TRPV3 in three distinct conformations: closed, heat-activated sensitized and open states. The heat-induced transformations of TRPV3 are accompanied by changes in the secondary structure of the S2-S3 linker and the N and C termini and represent a conformational wave that links these parts of the protein to a lipid occupying the vanilloid binding site. State-dependent differences in the behavior of bound lipids suggest their active role in thermo-TRP temperature-dependent gating. Our structural data, supported by physiological recordings and molecular dynamics simulations, provide an insight for understanding the molecular mechanism of temperature sensing.

Název v anglickém jazyce

Structural mechanism of heat-induced opening of a temperature-sensitive TRP channel

Popis výsledku anglicky

Numerous physiological functions rely on distinguishing temperature through temperature-sensitive transient receptor potential channels (thermo-TRPs). Although the function of thermo-TRPs has been studied extensively, structural determination of their heat- and cold-activated states has remained a challenge. Here, we present cryo-EM structures of the nanodisc-reconstituted wild-type mouse TRPV3 in three distinct conformations: closed, heat-activated sensitized and open states. The heat-induced transformations of TRPV3 are accompanied by changes in the secondary structure of the S2-S3 linker and the N and C termini and represent a conformational wave that links these parts of the protein to a lipid occupying the vanilloid binding site. State-dependent differences in the behavior of bound lipids suggest their active role in thermo-TRP temperature-dependent gating. Our structural data, supported by physiological recordings and molecular dynamics simulations, provide an insight for understanding the molecular mechanism of temperature sensing.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30103 - Neurosciences (including psychophysiology)

Projekt

<a href="/cs/project/GA19-03777S" target="_blank" >GA19-03777S: Molekulární mechanizmy regulace teplotně citlivých TRP iontových kanálů v nociceptivních neuronech</a><br>

Návaznosti

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

Rok uplatnění

2021

Kód důvěrnosti údajů

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

Název periodika

Nature Structural & Molecular Biology

ISSN

1545-9993

e-ISSN

1545-9985

Svazek periodika

28

Číslo periodika v rámci svazku

7

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

9

Strana od-do

564-572

Kód UT WoS článku

000670865500003

EID výsledku v databázi Scopus

2-s2.0-85109966115