Essential role of N-terminal SAM regions in STIM1 multimerization and function.

ABSTRACT: The single-pass transmembrane protein Stromal Interaction Molecule 1 (STIM1), located in the endoplasmic reticulum (ER) membrane, possesses two main functions: It senses the ER-Ca²⁺ concentration and directly binds to the store-operated Ca²⁺ channel Orai1 for its activation when Ca²⁺ recedes. At high resting ER-Ca²⁺ concentration, the ER-luminal STIM1 domain is kept monomeric but undergoes di/multimerization once stores are depleted. Luminal STIM1 multimerization is essential to unleash the STIM C-terminal binding site for Orai1 channels. However, structural basis of the luminal association sites has so far been elusive. Here, we employed molecular dynamics (MD) simulations and identified two essential di/multimerization segments, the α7 and the

SUBMITTER: Sallinger M 

PROVIDER: S-EPMC11127010 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature