Structural elements of stromal interaction molecule function

Cell Calcium. 2018 Jul:73:88-94. doi: 10.1016/j.ceca.2018.04.006. Epub 2018 Apr 18.


Stromal interaction molecule (STIM)-1 and -2 are multi-domain, single-pass transmembrane proteins involved in sensing changes in compartmentalized calcium (Ca2+) levels and transducing this cellular signal to Orai1 channel proteins. Our understanding of the molecular mechanisms underlying STIM signaling has been dramatically improved through available X-ray crystal and solution NMR structures. This high-resolution structural data has revealed that intricate intramolecular and intermolecular protein-protein interactions are involved in converting STIMs from the quiescent to activation-competent states. This review article summarizes the current high resolution structural data on specific EF-hand, sterile α motif and coiled-coil interactions which drive STIM function in the activation of Orai1 channels. Further, the work discusses the effects of post-translational modifications on the structure and function of STIMs. Future structural studies on larger STIM:Orai complexes will be critical to fully defining the molecular bases for STIM function and how post-translational modifications influence these mechanisms.

Keywords: Coiled-coil; EF-SAM; Glutathionylation; Glycosylation; Phosphorylation; STIM1; STIM2; Solution NMR; Stromal interaction molecule; X-ray crystallography.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cytosol / physiology
  • Humans
  • Neoplasm Proteins / chemistry*
  • Neoplasm Proteins / physiology*
  • Protein Binding / physiology
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Stromal Interaction Molecule 1 / chemistry*
  • Stromal Interaction Molecule 1 / physiology*
  • Stromal Interaction Molecule 2 / chemistry*
  • Stromal Interaction Molecule 2 / physiology*


  • Neoplasm Proteins
  • STIM1 protein, human
  • STIM2 protein, human
  • Stromal Interaction Molecule 1
  • Stromal Interaction Molecule 2

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