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

Structural elements of stromal interaction molecule function.

Author information

1
Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada.
2
Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada. Electronic address: mikura@uhnresearch.ca.
3
Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada. Electronic address: peter.stathopulos@schulich.uwo.ca.

Abstract

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

PMID:
29698850
DOI:
10.1016/j.ceca.2018.04.006
[Indexed for MEDLINE]

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