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STIM1 triggers a gating rearrangement at the extracellular mouth of the ORAI1 channel

Author

Listed:
  • Aparna Gudlur

    (La Jolla Institute for Allergy and Immunology)

  • Ariel Quintana

    (La Jolla Institute for Allergy and Immunology)

  • Yubin Zhou

    (La Jolla Institute for Allergy and Immunology
    Present address: Center for Translational Cancer Research, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas 77030, USA)

  • Nupura Hirve

    (La Jolla Institute for Allergy and Immunology)

  • Sahasransu Mahapatra

    (La Jolla Institute for Allergy and Immunology)

  • Patrick G. Hogan

    (La Jolla Institute for Allergy and Immunology)

Abstract

The ER-resident regulatory protein STIM1 triggers store-operated Ca2+ entry by direct interaction with the plasma membrane Ca2+ channel ORAI1. The mechanism of channel gating remains undefined. Here we establish that STIM1 gates the purified recombinant ORAI1 channel in vitro, and use Tb3+ luminescence and, separately, disulfide crosslinking to probe movements of the pore-lining helices. We show that interaction of STIM1 with the cytoplasmic face of the human ORAI1 channel elicits a conformational change near the external entrance to the pore, detectable at the pore Ca2+-binding residue E106 and the adjacent pore-lining residue V102. We demonstrate that a short nonpolar segment of the pore including V102 forms a barrier to ion flux in the closed channel, implicating the STIM1-dependent movement in channel gating. Our data explain the close coupling between ORAI1 channel gating and ion selectivity, and open a new avenue to dissect the gating, modulation and inactivation of ORAI-family channels.

Suggested Citation

  • Aparna Gudlur & Ariel Quintana & Yubin Zhou & Nupura Hirve & Sahasransu Mahapatra & Patrick G. Hogan, 2014. "STIM1 triggers a gating rearrangement at the extracellular mouth of the ORAI1 channel," Nature Communications, Nature, vol. 5(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6164
    DOI: 10.1038/ncomms6164
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