Abstract
Store-operated Ca 2+ entry through Orai1 channels is a primary mechanism for Ca 2+ entry in many cells and mediates numerous cellular effector functions ranging from gene transcription to exocytosis. Orai1 channels are amongst the most Ca 2+ -selective channels known and are activated by direct physical interactions with the endoplasmic reticulum Ca 2+ sensor stromal interaction molecule 1 (STIM1) in response to store depletion triggered by stimulation of a variety of cell surface G-protein coupled and tyrosine kinase receptors. Work in the last decade has revealed that the Orai1 gating process is highly cooperative and strongly allosteric, likely driven by a wave of interdependent conformational changes throughout the protein originating in the peripheral C-terminal ligand binding site and culminating in pore opening. In this review, we survey the structural and molecular features in Orai1 that contribute to channel gating and consider how they give rise to the unique biophysical fingerprint of Orai1 currents. (Figure presented.).
| Original language | English (US) |
|---|---|
| Journal | Journal of Physiology |
| DOIs | |
| State | Published - Jan 1 2019 |
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Keywords
- CRAC channel
- Calcium Channel
- Orai1
- STIM1
- ion channel gating
ASJC Scopus subject areas
- Physiology
Cite this
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Molecular basis of allosteric Orai1 channel activation by STIM1. / Yeung, Priscilla See Wai; Yamashita, Megumi; Prakriya, Murali.
In: Journal of Physiology, 01.01.2019.Research output: Contribution to journal › Review article
TY - JOUR
T1 - Molecular basis of allosteric Orai1 channel activation by STIM1
AU - Yeung, Priscilla See Wai
AU - Yamashita, Megumi
AU - Prakriya, Murali
PY - 2019/1/1
Y1 - 2019/1/1
N2 - Store-operated Ca 2+ entry through Orai1 channels is a primary mechanism for Ca 2+ entry in many cells and mediates numerous cellular effector functions ranging from gene transcription to exocytosis. Orai1 channels are amongst the most Ca 2+ -selective channels known and are activated by direct physical interactions with the endoplasmic reticulum Ca 2+ sensor stromal interaction molecule 1 (STIM1) in response to store depletion triggered by stimulation of a variety of cell surface G-protein coupled and tyrosine kinase receptors. Work in the last decade has revealed that the Orai1 gating process is highly cooperative and strongly allosteric, likely driven by a wave of interdependent conformational changes throughout the protein originating in the peripheral C-terminal ligand binding site and culminating in pore opening. In this review, we survey the structural and molecular features in Orai1 that contribute to channel gating and consider how they give rise to the unique biophysical fingerprint of Orai1 currents. (Figure presented.).
AB - Store-operated Ca 2+ entry through Orai1 channels is a primary mechanism for Ca 2+ entry in many cells and mediates numerous cellular effector functions ranging from gene transcription to exocytosis. Orai1 channels are amongst the most Ca 2+ -selective channels known and are activated by direct physical interactions with the endoplasmic reticulum Ca 2+ sensor stromal interaction molecule 1 (STIM1) in response to store depletion triggered by stimulation of a variety of cell surface G-protein coupled and tyrosine kinase receptors. Work in the last decade has revealed that the Orai1 gating process is highly cooperative and strongly allosteric, likely driven by a wave of interdependent conformational changes throughout the protein originating in the peripheral C-terminal ligand binding site and culminating in pore opening. In this review, we survey the structural and molecular features in Orai1 that contribute to channel gating and consider how they give rise to the unique biophysical fingerprint of Orai1 currents. (Figure presented.).
KW - CRAC channel
KW - Calcium Channel
KW - Orai1
KW - STIM1
KW - ion channel gating
UR - http://www.scopus.com/inward/record.url?scp=85065222433&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85065222433&partnerID=8YFLogxK
U2 - 10.1113/JP276550
DO - 10.1113/JP276550
M3 - Review article
C2 - 30950063
AN - SCOPUS:85065222433
JO - Journal of Physiology
JF - Journal of Physiology
SN - 0022-3751
ER -