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 CC1α1 and CC1α2 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.

• MeSH
• abnormální erytrocyty MeSH
• dyslexie genetika   MeSH
• HEK293 buňky MeSH
• ichtyóza genetika   MeSH
• kanály aktivované uvolněním vápníku metabolismus   MeSH
• klonování DNA MeSH
• konformace nukleové kyseliny MeSH
• lidé MeSH
• magnetická rezonanční spektroskopie MeSH
• metoda terčíkového zámku MeSH
• migréna genetika   MeSH
• mióza genetika   MeSH
• molekulární modely MeSH
• mutace genetika   MeSH
• nádorové proteiny genetika   MeSH
• protein ORAI1 genetika   MeSH
• protein STIM1 genetika   MeSH
• slezina abnormality   MeSH
• svalová únava genetika   MeSH
• trombocytopatie genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH