The quest to map STIM1 activation in granular detail

Cell Calcium. 2024 Nov:123:102946. doi: 10.1016/j.ceca.2024.102946. Epub 2024 Aug 23.

Abstract

The conformational change in STIM1 that communicates sensing of ER calcium-store depletion from the STIM ER-luminal domain to the STIM cytoplasmic region and ultimately to ORAI channels in the plasma membrane is broadly understood. However, the structural basis for the STIM luminal-domain dimerization that drives the conformational change has proven elusive. A recently published study has approached this question via molecular dynamics simulations. The report pinpoints STIM residues that may be part of a luminal-domain dimerization interface, and provides unexpected insight into how torsional movements of the STIM luminal domains might trigger release of the cytoplasmic SOAR/CAD domain from its resting tethers to the STIM CC1 segments.

Keywords: Calcium sensing; Conformation; Dimer; EFSAM; Interface; Molecular dynamics; STIM1.

MeSH terms

  • Animals
  • Calcium / metabolism
  • Endoplasmic Reticulum / metabolism
  • Humans
  • Molecular Dynamics Simulation
  • Neoplasm Proteins* / chemistry
  • Neoplasm Proteins* / metabolism
  • Stromal Interaction Molecule 1* / chemistry
  • Stromal Interaction Molecule 1* / metabolism

Substances

  • Calcium
  • Neoplasm Proteins
  • STIM1 protein, human
  • Stromal Interaction Molecule 1