Multiple weak brakes act in concert to control STIM1 and store-operated calcium entry.

ABSTRACT: Store-operated Ca²⁺ entry is a key signaling pathway controlled by the interaction of the ER Ca²⁺ sensor STIM1 with the Orai1 Ca²⁺ channel following ER Ca²⁺ depletion. To avoid generating pathological effects, STIM1 must remain mostly inactive under resting, ER-replete conditions yet respond rapidly and reversibly to changes in ER Ca²⁺ content. It is not well understood how these conflicting requirements are met. Here we combine single-molecule FRET measurements of full-length dimeric STIM1 in lipid membranes with an AlphaFold2 structural model to describe the structure and regulation of the resting state. We show that STIM1 activity is controlled by the combined operation of four relatively weak restraints, or brakes. The Ca²⁺

SUBMITTER: Qiu R 

PROVIDER: S-EPMC12718381 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature