Molecular basis of allosteric Orai1 channel activation by STIM1

Priscilla See Wai Yeung*, Megumi Yamashita, Murali Prakriya

*Corresponding author for this work

Research output: Contribution to journalReview article

1 Citation (Scopus)

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 languageEnglish (US)
JournalJournal of Physiology
DOIs
StatePublished - Jan 1 2019

Fingerprint

Exocytosis
Dermatoglyphics
Receptor Protein-Tyrosine Kinases
GTP-Binding Proteins
Endoplasmic Reticulum
Membrane Proteins
Binding Sites
Ligands
Genes
Proteins
Surveys and Questionnaires
Stromal Interaction Molecule 1

Keywords

  • CRAC channel
  • Calcium Channel
  • Orai1
  • STIM1
  • ion channel gating

ASJC Scopus subject areas

  • Physiology

Cite this

@article{c84d58e030d54dd09182857e1b7732de,
title = "Molecular basis of allosteric Orai1 channel activation by STIM1",
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.).",
keywords = "CRAC channel, Calcium Channel, Orai1, STIM1, ion channel gating",
author = "Yeung, {Priscilla See Wai} and Megumi Yamashita and Murali Prakriya",
year = "2019",
month = "1",
day = "1",
doi = "10.1113/JP276550",
language = "English (US)",
journal = "Journal of Physiology",
issn = "0022-3751",
publisher = "Wiley-Blackwell",

}

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 journalReview 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 -