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Spatiotemporal Control of Protein Activity through Optogenetic Allosteric Regulation
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Spatiotemporal Control of Protein Activity through Optogenetic Allosteric Regulation

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The remote allosteric control of Orai channel gating

Yandong Zhou1, Robert M Nwokonko1, James H Baraniak1

  • 1Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania, United States of America.

Plos Biology
|August 31, 2019
PubMed

Insights

Calcium signals are vital for cellular functions. New research reveals how Stromal Interaction Molecule (STIM) proteins activate Orai channels at the plasma membrane, clarifying calcium entry mechanisms.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biophysics

Background:

  • Calcium ions (Ca2+) are crucial intracellular messengers regulating diverse cellular processes like secretion, contraction, and gene transcription.
  • The Orai family of plasma membrane (PM) ion channels are the primary conduits for Ca2+ entry into cells.
  • Orai channels are activated by Stromal Interaction Molecule (STIM) proteins located in the endoplasmic reticulum (ER) membrane, a process occurring at ER-PM junctions.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which STIM proteins allosterically gate Orai channels.
  • To understand how STIM binding at the channel periphery remotely controls the opening of the Orai pore.

Main Methods:

  • Utilized crystallographic structural analyses to examine Orai channel structure.
  • Applied single-particle cryogenic electron microscopy (cryo-EM) to study Orai mutants mimicking STIM activation.
  • Investigated the interaction between STIM proteins and Orai channels.

Main Results:

  • Structural analyses provided insights into the hexameric core of Orai channels.
  • New structural data illuminates the open state of the Orai channel.
  • The study offers a molecular basis for how STIM proteins remotely control Orai channel gating.

Conclusions:

  • The findings advance our understanding of the activation mechanism of Orai channels by STIM proteins.
  • This research clarifies the structural basis of STIM-mediated allosteric gating of Orai channels.
  • The results provide a foundation for further investigation into calcium signaling pathways.

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