Interhelical interactions within the STIM1 CC1 domain modulate CRAC channel activation

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60076658%3A12310%2F21%3A43904251" target="_blank" >RIV/60076658:12310/21:43904251 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.nature.com/articles/s41589-020-00672-8" target="_blank" >https://www.nature.com/articles/s41589-020-00672-8</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41589-020-00672-8" target="_blank" >10.1038/s41589-020-00672-8</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Interhelical interactions within the STIM1 CC1 domain modulate CRAC channel activation

Popis výsledku v původním jazyce

The calcium release activated calcium channel is activated by the endoplasmic reticulum-resident calcium sensor protein STIM1. On activation, STIM1 C terminus changes from an inactive, tight to an active, extended conformation. A coiled-coil clamp involving the CC1 and CC3 domains is essential in controlling STIM1 activation, with CC1 as the key entity. The nuclear magnetic resonance-derived solution structure of the CC1 domain represents a three-helix bundle stabilized by interhelical contacts, which are absent in the Stormorken disease-related STIM1 R304W mutant. Two interhelical sites between the CC1 alpha(1) and CC1 alpha(2) helices are key in controlling STIM1 activation, affecting the balance between tight and extended conformations. Nuclear magnetic resonance-directed mutations within these interhelical interactions restore the physiological, store-dependent activation behavior of the gain-of-function STIM1 R304W mutant. This study reveals the functional impact of interhelical interactions within the CC1 domain for modifying the CC1-CC3 clamp strength to control the activation of STIM1.

Název v anglickém jazyce

Interhelical interactions within the STIM1 CC1 domain modulate CRAC channel activation

Popis výsledku anglicky

The calcium release activated calcium channel is activated by the endoplasmic reticulum-resident calcium sensor protein STIM1. On activation, STIM1 C terminus changes from an inactive, tight to an active, extended conformation. A coiled-coil clamp involving the CC1 and CC3 domains is essential in controlling STIM1 activation, with CC1 as the key entity. The nuclear magnetic resonance-derived solution structure of the CC1 domain represents a three-helix bundle stabilized by interhelical contacts, which are absent in the Stormorken disease-related STIM1 R304W mutant. Two interhelical sites between the CC1 alpha(1) and CC1 alpha(2) helices are key in controlling STIM1 activation, affecting the balance between tight and extended conformations. Nuclear magnetic resonance-directed mutations within these interhelical interactions restore the physiological, store-dependent activation behavior of the gain-of-function STIM1 R304W mutant. This study reveals the functional impact of interhelical interactions within the CC1 domain for modifying the CC1-CC3 clamp strength to control the activation of STIM1.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2021

Kód důvěrnosti údajů

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

Název periodika

Nature Chemical Biology

ISSN

1552-4450

e-ISSN

—

Svazek periodika

17

Číslo periodika v rámci svazku

2

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

9

Strana od-do

196-204

Kód UT WoS článku

000583964700004

EID výsledku v databázi Scopus

2-s2.0-85093962070