Orai channel pore properties and gating by STIM

Implications from the orai crystal structure

Brad S. Rothberg, Youjun Wang, Donald Gill

Research output: Contribution to journalReview article

43 Citations (Scopus)

Abstract

The Orai channels are unusual, yet prominent, calcium (Ca2+) signal mediators in most cell types. Orai proteins are structurally unique, having little sequence homology with other ion channels. They are also functionally unique with exceedingly high selectivity for Ca2+, mediating both short-term Ca2+ homeostasis and long-term Ca 2+ signals important for transcriptional control. Operating in the plasma membrane (PM), Orai channel regulation is unprecedented among ion channels; channel gating occurs through an elaborate intermembrane coupling with stromal interaction molecule (STIM) proteins in the endoplasmic reticulum (ER). STIM proteins function as sensors of Ca2+ stored in the ER lumen and translocate into ER-PM junctions to tether and activate Orai channels when ER Ca2+ concentration decreases. Crystallization studies reveal an unexpected hexameric structure for the Orai channel and provide important insights into the pore architecture, the structural basis of its unusual cation selectivity, and how channel gating occurs through its coupling with STIM proteins.

Original languageEnglish (US)
JournalScience Signaling
Volume6
Issue number267
DOIs
StatePublished - Mar 19 2013

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Endoplasmic Reticulum
Crystal structure
Ion Channels
Molecules
Cell membranes
Proteins
Cell Membrane
Sequence Homology
Crystallization
Cations
Homeostasis
Calcium
Stromal Interaction Molecules
Sensors

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

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Orai channel pore properties and gating by STIM : Implications from the orai crystal structure. / Rothberg, Brad S.; Wang, Youjun; Gill, Donald.

In: Science Signaling, Vol. 6, No. 267, 19.03.2013.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Orai channel pore properties and gating by STIM

T2 - Implications from the orai crystal structure

AU - Rothberg, Brad S.

AU - Wang, Youjun

AU - Gill, Donald

PY - 2013/3/19

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AB - The Orai channels are unusual, yet prominent, calcium (Ca2+) signal mediators in most cell types. Orai proteins are structurally unique, having little sequence homology with other ion channels. They are also functionally unique with exceedingly high selectivity for Ca2+, mediating both short-term Ca2+ homeostasis and long-term Ca 2+ signals important for transcriptional control. Operating in the plasma membrane (PM), Orai channel regulation is unprecedented among ion channels; channel gating occurs through an elaborate intermembrane coupling with stromal interaction molecule (STIM) proteins in the endoplasmic reticulum (ER). STIM proteins function as sensors of Ca2+ stored in the ER lumen and translocate into ER-PM junctions to tether and activate Orai channels when ER Ca2+ concentration decreases. Crystallization studies reveal an unexpected hexameric structure for the Orai channel and provide important insights into the pore architecture, the structural basis of its unusual cation selectivity, and how channel gating occurs through its coupling with STIM proteins.

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