The STIM-Orai Pathway: STIM-Orai Structures: Isolated and in Complex

Adv Exp Med Biol. 2017:993:15-38. doi: 10.1007/978-3-319-57732-6_2.


Considerable progress has been made elucidating the molecular mechanisms of calcium (Ca2+) sensing by stromal interaction molecules (STIMs) and the basis for Orai channel activity. This chapter focuses on the available high-resolution structural details of STIM and Orai proteins with respect to the regulation of store-operated Ca2+ entry (SOCE). Solution structures of the Ca2+-sensing domains of STIM1 and STIM2 are reviewed in detail, crystal structures of cytosolic coiled-coil STIM fragments are discussed, and an overview of the closed Drosophila melanogaster Orai hexameric structure is provided. Additionally, we highlight structures of human Orai1 N-terminal and C-terminal domains in complex with calmodulin and human STIM1, respectively. Ultimately, the accessible structural data are discussed in terms of potential mechanisms of action and cohesiveness with functional observations.

Keywords: Calmodulin; Orai1; Solution nuclear magnetic resonance spectroscopy; Store-operated calcium entry; Stromal interaction molecules; Structural mechanisms; X-ray crystallography.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Calcium / metabolism
  • Calcium Signaling / physiology*
  • Calmodulin / metabolism
  • Cytosol / metabolism
  • Humans
  • ORAI1 Protein / metabolism*
  • Stromal Interaction Molecule 1 / metabolism*
  • Stromal Interaction Molecule 2 / metabolism*


  • Calmodulin
  • ORAI1 Protein
  • Stromal Interaction Molecule 1
  • Stromal Interaction Molecule 2
  • Calcium