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

  • Jinhui Zhu
  • Qingping Feng
  • Peter B. StathopulosEmail author
Chapter
Part of the Advances in Experimental Medicine and Biology book series (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.

Keywords

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

Notes

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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Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Jinhui Zhu
    • 1
  • Qingping Feng
    • 1
  • Peter B. Stathopulos
    • 1
    Email author
  1. 1.Department of Physiology and Pharmacology, Schulich School of Medicine and DentistryWestern UniversityLondonCanada

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