Structural elements of stromal interaction molecule function. (July 2018)

• Record Type: Journal Article
• Authors: Novello, Matthew J.; Zhu, Jinhui; Feng, Qingping; Ikura, Mitsuhiko; Stathopulos, Peter B.
• Is Part Of: Cell calcium. Volume 73(2018)
• Page Start: 88
• Page End: 94
• Publication Date: 2018-07
• Subjects: Stromal interaction molecule -- STIM1 -- STIM2 -- X-ray crystallography -- Solution NMR -- Coiled-coil -- EF-SAM -- Phosphorylation -- Glycosylation -- Glutathionylation; Calcium -- Metabolism -- Periodicals; Vertebrates -- Physiology -- Periodicals; Calcium -- Physiological effect -- Periodicals; Cell physiology -- Periodicals; Calcium in the body -- Periodicals; 572.516
• DOI: 10.1016/j.ceca.2018.04.006
• Languages: English
• ISSNs: 0143-4160

Abstract

Graphical abstract: Highlights: The luminal domains maintain STIM quiescence via EF-hand:SAM domain interactions. A dynamic exchange of cytosolic coiled-coil interactions underlies STIM1 activation. Glycosyl-, glutathionyl- and phosphorylation regulate STIM structure and function. Abstract: Stromal interaction molecule (STIM)-1 and -2 are multi-domain, single-pass transmembrane proteins involved in sensing changes in compartmentalized calcium (Ca 2+ ) 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.