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

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Store-Operated Ca²⁺ Entry (SOCE) Pathways

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 993))

Abstract

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.

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Acknowledgments

This work was supported by a Natural Sciences and Engineering Research Council of Canada Discovery Grant to P.B.S. and Canadian Institutes of Health Research Operating Grant to Q.F., P.B.S., and W.Y.L. We thank Mitsuhiko Ikura for his invaluable contributions in preparing the first edition version of this chapter and Steve Chung for his careful review of the manuscript.

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Authors and Affiliations

  1. Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada, N6A 5C1

    Jinhui Zhu, Qingping Feng & Peter B. Stathopulos

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  1. Jinhui Zhu
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  2. Qingping Feng
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  3. Peter B. Stathopulos
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Correspondence to Peter B. Stathopulos .

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  1. Institute of Biophysics, Medical University of Graz, Graz, Austria

    Klaus Groschner

  2. Institute of Molecular Biology and Biochemistry, Medical University of Graz, Graz, Austria

    Wolfgang F. Graier

  3. Institute of Biophysics, Johannes Kepler University Linz, Linz, Austria

    Christoph Romanin

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Zhu, J., Feng, Q., Stathopulos, P.B. (2017). The STIM-Orai Pathway: STIM-Orai Structures: Isolated and in Complex. In: Groschner, K., Graier, W., Romanin, C. (eds) Store-Operated Ca²⁺ Entry (SOCE) Pathways. Advances in Experimental Medicine and Biology, vol 993. Springer, Cham. https://doi.org/10.1007/978-3-319-57732-6_2

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