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Live Cell Calcium Imaging Combined with siRNA Mediated Gene Silencing Identifies Ca2+ Leak Channels in the ER Membrane and their Regulatory Mechanisms
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Structural aspects of calcium-release activated calcium channel function.

Peter B Stathopulos1, Mitsuhiko Ikura1

  • 1Princess Margaret Cancer Centre; Department of Medical Biophysics; University of Toronto; Toronto, ON, Canada.

Channels (Austin, Tex.)
|November 12, 2013
PubMed
Summary
This summary is machine-generated.

Store-operated calcium entry (SOCE) involves STIM proteins sensing calcium levels and Orai proteins forming channels. Structural data reveals insights into CRAC channel mechanisms and function.

Keywords:
Orai channel proteinscalcium release activated calciumcalmodulinstore operated calcium entrystromal interaction molecules

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Area of Science:

  • Molecular Biology
  • Cell Physiology
  • Biochemistry

Background:

  • Store-operated calcium entry (SOCE) is crucial for sustained cytosolic calcium elevation.
  • This process involves stromal interaction molecules (STIMs) and Orai proteins.
  • STIMs sense calcium in the ER/SR, signaling Orai channels on the plasma membrane to open.

Purpose of the Study:

  • To review high-resolution structural information of molecular components mediating SOCE.
  • To focus on structural data of STIM and Orai proteins.
  • To discuss structural findings in relation to CRAC channel mechanisms.

Main Methods:

  • Review of existing high-resolution structural data.
  • Analysis of solution structures of luminal STIM Ca(2+) sensing domains.
  • Examination of crystal structures of cytosolic STIM fragments and Orai proteins.

Main Results:

  • High-resolution structures of STIM and Orai components are available.
  • Structural data includes STIM Ca(2+) sensing domains and Orai channel structures.
  • A closed hexameric Orai structure and an Orai1-calmodulin complex structure are discussed.

Conclusions:

  • Structural data provides insights into the molecular mechanisms of SOCE.
  • The findings offer a basis for understanding CRAC channel function.
  • Structural information is consistent with functional observations of calcium signaling.