Structures reveal opening of the store-operated calcium channel Orai

Xiaowei HouStephen B Long


The store-operated calcium (Ca2+) channel Orai governs Ca2+ influx through the plasma membrane of many non-excitable cells in metazoans. The channel opens in response to the depletion of Ca2+ stored in the endoplasmic reticulum (ER). Loss- and gain-of-function mutants of Orai cause disease. Our previous work revealed the structure of Orai with a closed pore. Here, using a gain-of-function mutation that constitutively activates the channel, we present an X-ray structure of Drosophila melanogaster Orai in an open conformation. Well-defined electron density maps reveal that the pore is dramatically dilated on its cytosolic side in comparison to the slender closed pore. Cations and anions bind in different regions of the open pore, informing mechanisms for ion permeation and Ca2+ selectivity. Opening of the pore requires the release of cytosolic latches. Together with additional X-ray structures of an unlatched-but-closed conformation, we propose a sequence for store-operated activation.


Jun 1, 1982·The Journal of Cell Biology·J V KilmartinC Milstein
Jul 1, 1995·Pflügers Archiv : European journal of physiology·Markus Hoth
Oct 3, 1998·Acta Crystallographica. Section D, Biological Crystallography·Axel T BrungerG L Warren
Sep 27, 2002·Biophysical Journal·Roxana E GeorgescuMarilyn R Gunner
Dec 10, 2002·Annual Review of Physiology·William A Sather, Edwin W McCleskey
May 4, 2005·The Journal of Cell Biology·Jack RoosKenneth A Stauderman
Jul 9, 2005·Science·Stephen B LongRoderick Mackinnon
Jul 12, 2005·Current Biology : CB·Jen LiouTobias Meyer
Jun 6, 2006·Proceedings of the National Academy of Sciences of the United States of America·Shenyuan L ZhangMichael D Cahalan
Aug 22, 2006·Nature·Murali PrakriyaPatrick G Hogan
Aug 31, 2006·The Journal of General Physiology·Murali Prakriya, Richard S Lewis
Sep 19, 2006·Current Biology : CB·Monika VigReinhold Penner
Dec 19, 2006·Methods in Molecular Biology·Clemens VonrheinGérard Bricogne
Aug 19, 2007·The Journal of Biological Chemistry·Zhengzheng LiTao Xu
Dec 18, 2007·Cell·D E Clapham
Jan 12, 2008·The Journal of Biological Chemistry·M MuikChristoph Romanin
Oct 4, 2008·The Journal of Physiology·Laura Navarro-BorellyMurali Prakriya
Feb 3, 2009·Nature Cell Biology·Joseph P YuanShmuel Muallem
May 13, 2009·Biochemical and Biophysical Research Communications·Takumi KawasakiStefan Feske
Dec 19, 2009·Proceedings of the National Academy of Sciences of the United States of America·Beth A McNallyMurali Prakriya
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Wolfgang Kabsch
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Paul D AdamsPeter H Zwart
Mar 3, 2010·Proceedings of the National Academy of Sciences of the United States of America·Yubin ZhouPatrick G Hogan
Mar 24, 2010·Annual Review of Immunology·Patrick G HoganAnjana Rao
Apr 9, 2010·Nature·Gunnar F SchröderAxel T Brunger
Apr 13, 2010·Acta Crystallographica. Section D, Biological Crystallography·P EmsleyK Cowtan
Dec 1, 2010·The Journal of General Physiology·Annette LisReinhold Penner
Oct 12, 2011·Proceedings of the National Academy of Sciences of the United States of America·Shenyuan L ZhangMichael D Cahalan
Jan 27, 2012·Nature·Beth A McNallyMurali Prakriya
Mar 28, 2012·Proceedings of the National Academy of Sciences of the United States of America·Xue YangYuequan Shen
May 26, 2012·Science·P Andrew Karplus, Kay Diederichs
Jun 12, 2012·Structure·Axel T BrungerGunnar F Schröder
Nov 28, 2012·Science·Xiaowei HouStephen B Long
Jul 23, 2013·Nature·Tsai-Wen ChenDouglas S Kim
Dec 20, 2013·Nature Communications·Peter B StathopulosMitsuhiko Ikura


Apr 23, 2019·PLoS Biology·Xiaofen LiuYuequan Shen
Apr 6, 2019·The Journal of Physiology·Priscilla See-Wai YeungMurali Prakriya
Dec 10, 2019·The Journal of General Physiology·Megumi YamashitaMurali Prakriya
Sep 27, 2019·Current Drug Targets·Sampath Bhuvaneshwari, Kavitha Sankaranarayanan
Feb 29, 2020·Journal of Cell Science·Liling NiuQian Wang
Oct 2, 2019·Cold Spring Harbor Perspectives in Biology·Richard S Lewis
Mar 25, 2019·European Biophysics Journal : EBJ·Adéla KrizovaIsabella Derler
Dec 12, 2019·Journal of Cell Science·Dalia AlansaryNiels de Jonge
Aug 28, 2020·Nature·Chunfu XuDavid Baker
May 28, 2020·International Journal of Molecular Sciences·Megan NoblePeter B Stathopulos
Jun 27, 2019·Proceedings of the National Academy of Sciences of the United States of America·Shanlin RaoMark S P Sansom
May 25, 2020·Medical Microbiology and Immunology·Rebecca L GavinMichael G Tomlinson
Oct 31, 2020·ELife·Priscilla S-W YeungMurali Prakriya
Sep 24, 2020·Annual Review of Pharmacology and Toxicology·Daniel BakowskiAnant B Parekh
Dec 15, 2020·Cell Calcium·Daniel BonhenryRainer Schindl
Dec 29, 2020·The Journal of Biological Chemistry·Adéla KrizovaIsabella Derler
Sep 22, 2020·Current Opinion in Physiology·James H BaraniakDonald L Gill
Jan 8, 2021·Current Opinion in Physiology·Matthias SallingerIrene Frischauf
Jan 13, 2021·International Journal of Molecular Sciences·Adéla KrizovaIsabella Derler
Jan 29, 2021·Scientific Reports·Rawad HodeifyKhaled Machaca
Feb 14, 2021·Cell Calcium·Murali PrakriyaMegumi Yamashita
Jan 13, 2021·Nature Communications·Lian HeYubin Zhou
Mar 3, 2021·Journal of Clinical Immunology·Fang YuKhaled Machaca
Mar 3, 2021·Proceedings of the National Academy of Sciences of the United States of America·Yihan ShenColin W Taylor
Sep 21, 2020·Journal of Structural Biology·Nate YoderEric Gouaux

Methods Mentioned

Flow cytometry
ion exchange chromatography
gel filtration
size exclusion chromatography

Related Concepts

Trending Feeds


Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Hereditary Sensory Autonomic Neuropathy

Hereditary Sensory Autonomic Neuropathies are a group of inherited neurodegenerative disorders characterized clinically by loss of sensation and autonomic dysfunction. Here is the latest research on these neuropathies.

Glut1 Deficiency

Glut1 deficiency, an autosomal dominant, genetic metabolic disorder associated with a deficiency of GLUT1, the protein that transports glucose across the blood brain barrier, is characterized by mental and motor developmental delays and infantile seizures. Follow the latest research on Glut1 deficiency with this feed.

Regulation of Vocal-Motor Plasticity

Dopaminergic projections to the basal ganglia and nucleus accumbens shape the learning and plasticity of motivated behaviors across species including the regulation of vocal-motor plasticity and performance in songbirds. Discover the latest research on the regulation of vocal-motor plasticity here.

Neural Activity: Imaging

Imaging of neural activity in vivo has developed rapidly recently with the advancement of fluorescence microscopy, including new applications using miniaturized microscopes (miniscopes). This feed follows the progress in this growing field.

Nodding Syndrome

Nodding Syndrome is a neurological and epileptiform disorder characterized by psychomotor, mental, and growth retardation. Discover the latest research on Nodding Syndrome here.

LRRK2 & Microtubules

Mutations in the LRRK2 gene are risk-factors for developing Parkinson’s disease (PD). LRRK2 mutations in PD have been shown to enhance its association with microtubules. Here is the latest research.