Structural rearrangements underlying the activation of STIM1 by ER calcium depletion.

ABSTRACT: In resting cells, STIM1, the dimeric ER Ca²⁺ sensor that controls store-operated Ca²⁺ entry (SOCE), is held in a Ca²⁺-bound inactive state by multiple intramolecular restraints, or brakes. Receptor-evoked release of Ca²⁺ from the ER causes a large conformational change in STIM1 that releases the brakes and exposes the CRAC activation domain (CAD), enabling it to bind and open store-operated Orai1 channels in the plasma membrane. We performed single-molecule FRET measurements with purified STIM1 to better understand how Ca²⁺ release from the luminal domain of STIM1 drives the conformational changes in the cytosolic domain that underlie CAD release. We find that Ca²⁺ removal releases the CAD from CC1α1 (the 'CC1 clamp') withou

SUBMITTER: Qiu R 

PROVIDER: S-EPMC12871627 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature