ArticleScientific reports2016
Thiol dependent intramolecular locking of Orai1 channels.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed, 37 citations in OpenAlex.
- Mechanistic insights into Orai dynamics during pore opening.Channels (Austin, Tex.) · 2026Review
- The intracellular localization and the ionic permeation of TRPV6 triggers chronic pancreatitis, skeletal dysplasia and is connected to mucolipidosis type II.Cell communication and signaling : CCS · 2025Article
- Crosstalk between calcium and reactive oxygen species signaling in cancer revisited.Cell calcium · 2025Review
- Store-operated calcium entry is reduced in spastin-linked hereditary spastic paraplegia.Brain : a journal of neurology · 2022Article
- Control of STIM and Orai function by post-translational modifications.Cell calcium · 2022Review
- A longer isoform of Stim1 is a negative SOCE regulator but increases cAMP-modulated NFAT signaling.EMBO reports · 2022Article
- Extracellular cysteines C226 and C232 mediate hydrogen sulfide-dependent inhibition of Orai3-mediated store-operated calcium entry.American journal of physiology. Cell physiology · 2022Article
- STIM and Orai Mediated Regulation of Calcium Signaling in Age-Related Diseases.Frontiers in aging · 2022Review
- Article
- Reactive Oxygen Species and Endothelial CaInternational journal of molecular sciences · 2021Review
- Isoform-Specific Properties of Orai Homologues in Activation, Downstream Signaling, Physiology and Pathophysiology.International journal of molecular sciences · 2021Review
- The Orai Pore Opening Mechanism.International journal of molecular sciences · 2021Review
- Orai channels: key players in CaCurrent opinion in physiology · 2020Article
- Calcium regulation of T cell metabolismCurrent opinion in physiology · 2020Article
- Structural features of STIM and Orai underlying store-operated calcium entry.Current opinion in cell biology · 2019Review
- Review
- Store-Operated Calcium Entry Contributes to Cisplatin-Induced Cell Death in Non-Small Cell Lung Carcinoma.Cancers · 2019Article
- Linking ploidy level with salinity tolerance: NADPH-dependent 'ROS-Ca2+ hub' in the spotlight.Journal of experimental botany · 2019Article
- ORAI1 channel gating and selectivity is differentially altered by natural mutations in the first or third transmembrane domain.The Journal of physiology · 2019Article
- The role of CaCell calcium · 2018Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Store-operated Ca(2+) entry mediated by STIM1-gated Orai1 channels is essential to activate immune cells and its inhibition or gain-of-function can lead to immune dysfunction and other pathologies. Reactive oxygen species interacting with cysteine residues can alter protein function. Pretreatment of the Ca(2+) selective Orai1 with the oxidant H2O2 reduces ICRAC with C195, distant to the pore, being its major redox sensor. However, the mechanism of inhibition remained elusive. Here we combine experimental and theoretical approaches and show that oxidation of Orai1 leads to reduced subunit interaction, slows diffusion and that either oxidized C195 or its oxidomimetic mutation C195D located at the exit of transmembrane helix 3 virtually eliminates channel activation by intramolecular interaction with S239 of transmembrane helix 4, thereby locking the channel in a closed conformation. Our results demonstrate a novel mechanistic model for ROS-mediated inhibition of Orai1 and identify a candidate residue for pharmaceutical intervention.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.