ArticlePLoS biology2019
Molecular understanding of calcium permeation through the open Orai channel.
Article in PLoS biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed.
- Mechanistic insights into Orai dynamics during pore opening.Channels (Austin, Tex.) · 2026Review
- Research progress on the role and mechanism of STIM and Orai protein-mediated store-operated calcium entry in cardiovascular diseases.Channels (Austin, Tex.) · 2026Review
- Evolutionarily conserved hydrophobicity and sterics in TM3/TM4 balance Orai1 pore opening.Protein science : a publication of the Protein Society · 2026Article
- The Nanodisc System for Investigating Protein-Lipid Interactions.Methods in molecular biology (Clifton, N.J.) · 2026Review
- Article
- Store-operated calcium entry-based targets for novel cancer therapeutic development.The Journal of pharmacology and experimental therapeutics · 2025Review
- Water in peripheral TM-interfaces of Orai1-channels triggers pore opening.Communications biology · 2024Article
- ORAI CaBiomolecules · 2024Review
- Synthetic Biology Meets CaCells · 2024Review
- Rectifying artificial nanochannels with multiple interconvertible permeability states.Nature communications · 2024Article
- Side-by-side comparison of published small molecule inhibitors against thapsigargin-induced store-operated Ca2+ entry in HEK293 cells.PloS one · 2024Article
- STIM1 in tumor cell death: angel or devil?Cell death discovery · 2023Review
- Molecular basis of MgNature communications · 2023Article
- Photocrosslinking-induced CRAC channel-like Orai1 activation independent of STIM1.Nature communications · 2023Article
- A pathogenic human Orai1 mutation unmasks STIM1-independent rapid inactivation of Orai1 channels.eLife · 2023Article
- CRAC and SK Channels: Their Molecular Mechanisms Associated with Cancer Cell Development.Cancers · 2022Review
- The Role of Lipids in CRAC Channel Function.Biomolecules · 2022Review
- Highlighting the Multifaceted Role of Orai1 N-Terminal- and Loop Regions for Proper CRAC Channel Functions.Cells · 2022Review
- Simulation and Machine Learning Methods for Ion-Channel Structure Determination, Mechanistic Studies and Drug Design.Frontiers in pharmacology · 2022Review
- Article
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10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Orai channel is characterized by voltage independence, low conductance, and high Ca2+ selectivity and plays an important role in Ca2+ influx through the plasma membrane (PM). How the channel is activated and promotes Ca2+ permeation is not well understood. Here, we report the crystal structure and cryo-electron microscopy (cryo-EM) reconstruction of a Drosophila melanogaster Orai (dOrai) mutant (P288L) channel that is constitutively active according to electrophysiology. The open state of the Orai channel showed a hexameric assembly in which 6 transmembrane 1 (TM1) helices in the center form the ion-conducting pore, and 6 TM4 helices in the periphery form extended long helices. Orai channel activation requires conformational transduction from TM4 to TM1 and eventually causes the basic section of TM1 to twist outward. The wider pore on the cytosolic side aggregates anions to increase the potential gradient across the membrane and thus facilitate Ca2+ permeation. The open-state structure of the Orai channel offers insights into channel assembly, channel activation, and Ca2+ permeation.
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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.