ArticleProceedings of the National Academy of Sciences of the United States of America2009
Structural determinants of ion permeation in CRAC channels.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.
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Who cites it
93 citing papers in PubMed.
- Mechanistic insights into Orai dynamics during pore opening.Channels (Austin, Tex.) · 2026Review
- Store-Operated Calcium Channels in the Nervous System.Annual review of physiology · 2025Review
- Side-by-side comparison of published small molecule inhibitors against thapsigargin-induced store-operated Ca2+ entry in HEK293 cells.PloS one · 2024Article
- ORAI Calcium Channels: Regulation, Function, Pharmacology, and Therapeutic Targets.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Regulatory mechanisms controlling store-operated calcium entry.Frontiers in physiology · 2023Review
- Highlighting the Multifaceted Role of Orai1 N-Terminal- and Loop Regions for Proper CRAC Channel Functions.Cells · 2022Review
- Isoform-Specific Properties of Orai Homologues in Activation, Downstream Signaling, Physiology and Pathophysiology.International journal of molecular sciences · 2021Review
- Novel ORAI1 Mutation Disrupts Channel Trafficking Resulting in Combined Immunodeficiency.Journal of clinical immunology · 2021Article
- An open pore structure of the Orai channel, finally.Cell calcium · 2021Article
- The Orai Pore Opening Mechanism.International journal of molecular sciences · 2021Review
- The Impact of Mutation L138F/L210F on the Orai Channel: A Molecular Dynamics Simulation Study.Frontiers in molecular biosciences · 2021Article
- Interrogating permeation and gating of Orai channels using chemical modification of cysteine residues.Methods in enzymology · 2021Article
- ORAI1 CaFrontiers in cell and developmental biology · 2021Review
- Molecular Choreography and Structure of CaMembranes · 2020Review
- Cryo-EM structure of the calcium release-activated calcium channel Orai in an open conformation.eLife · 2020Article
- Article
- Molecular basis of allosteric Orai1 channel activation by STIM1.The Journal of physiology · 2020Review
- Targeting Calcium Release-activated Calcium Channel Is Not Sufficient to Prevent Rejection in Nonhuman Primate Kidney Transplantation.Transplantation · 2020Article
- The basic residues in the Orai1 channel inner pore promote opening of the outer hydrophobic gate.The Journal of general physiology · 2020Article
- Critical parameters maintaining authentic CRAC channel hallmarks.European biophysics journal : EBJ · 2019Review
33 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors.
Funding
Abstract
CRAC channels generate Ca(2+) signals critical for the activation of immune cells and exhibit an intriguing pore profile distinguished by extremely high Ca(2+) selectivity, low Cs(+) permeability, and small unitary conductance. To identify the ion conduction pathway and gain insight into the structural bases of these permeation characteristics, we introduced cysteine residues in the CRAC channel pore subunit, Orai1, and probed their accessibility to various thiol-reactive reagents. Our results indicate that the architecture of the ion conduction pathway is characterized by a flexible outer vestibule formed by the TM1-TM2 loop, which leads to a narrow pore flanked by residues of a helical TM1 segment. Residues in TM3, and specifically, E190, a residue considered important for ion selectivity, are not close to the pore. Moreover, the outer vestibule does not significantly contribute to ion selectivity, implying that Ca(2+) selectivity is conferred mainly by E106. The ion conduction pathway is sufficiently narrow along much of its length to permit stable coordination of Cd(2+) by several TM1 residues, which likely explains the slow flux of ions within the restrained geometry of the pore. These results provide a structural framework to understand the unique permeation properties of CRAC channels.
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