ArticleThe Journal of biological chemistry2013
Differential roles of the C and N termini of Orai1 protein in interacting with stromal interaction molecule 1 (STIM1) for Ca2+ release-activated Ca2+ (CRAC) channel activation.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 91 citations in OpenAlex.
- Astrocyte store-operated calcium entry is required for centrally mediated neuropathic pain.Pain reports · 2026Article
- Store-operated calcium entry-based targets for novel cancer therapeutic development.The Journal of pharmacology and experimental therapeutics · 2025Review
- Regulatory mechanisms controlling store-operated calcium entry.Frontiers in physiology · 2023Review
- The roles of transmembrane family proteins in the regulation of store-operated CaCellular and molecular life sciences : CMLS · 2022Review
- Analysis ofAmerican journal of physiology. Heart and circulatory physiology · 2022Article
- Highlighting the Multifaceted Role of Orai1 N-Terminal- and Loop Regions for Proper CRAC Channel Functions.Cells · 2022Review
- High-Calcium Microenvironment during the Development of Kidney Calculi Can Promote Phenotypic Transformation of NRK-52E Cells by Inhibiting the Expression of Stromal Interaction Molecule-1.BioMed research international · 2022Article
- ORF3a of SARS-CoV-2 promotes lysosomal exocytosis-mediated viral egress.Developmental cell · 2021Article
- Immune Synapse Residency of Orai1 Alters CaInternational journal of molecular sciences · 2021Article
- Regulation of Store-Operated CaCells · 2021Review
- Orai channel C-terminal peptides are key modulators of STIM-Orai coupling and calcium signal generation.Cell reports · 2021Article
- Endoplasmic Reticulum-Plasma Membrane Contact Sites as an Organizing Principle for Compartmentalized Calcium and cAMP Signaling.International journal of molecular sciences · 2021Review
- Transmembrane Domain 3 (TM3) Governs Orai1 and Orai3 Pore Opening in an Isoform-Specific Manner.Frontiers in cell and developmental biology · 2021Article
- Article
- Proteins Interacting with STIM1 and Store-Operated CaProgress in molecular and subcellular biology · 2021Review
- Cryo-EM structure of the calcium release-activated calcium channel Orai in an open conformation.eLife · 2020Article
- The Intricate Coupling Between STIM Proteins and Orai Channels.Current opinion in physiology · 2020Article
- Molecular basis of allosteric Orai1 channel activation by STIM1.The Journal of physiology · 2020Review
- Toward a Model for Activation of Orai Channel.iScience · 2019Article
- Investigation of novel variations of ORAI1 gene and their association with Kawasaki disease.Journal of human genetics · 2019Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The entry of extracellular Ca(2+), which is mediated by Ca(2+) release-activated Ca(2+) (CRAC) channels, is essential for T cell activation and the normal functioning of other immune cells. Although the molecular components of CRAC channels, the Orai1 pore-forming subunit and the STIM1-activating subunit have been recently identified, the gating mechanism by which Orai1 channels conduct Ca(2+) entry upon Orai1-STIM1 interaction following Ca(2+) store release remains elusive. Herein, we show that C-terminal truncations or point mutations prevented Orai1 from binding to STIM1 and subsequent channel opening. In contrast, an Orai1 mutant with an N-terminal truncation interacted with but failed to be activated by STIM1. Moreover, Orai1 channels with C-terminal disruption, but not N-terminal truncation, could be gated by fused functional domains of STIM1. Interestingly, the channel activities of Orai1 mutants carrying either an N-terminal or a C-terminal truncation were restored by a methionine mutation at the putative gating hinge, the conserved Gly-98 site in the first transmembrane segment (TM1) of Orai1. Collectively, these results support a stepwise gating mechanism of STIM1-operated Orai1 channels; the initial binding between STIM1 and the C terminus of Orai1 docks STIM1 onto the N terminus of Orai1 to initiate conformational changes of the pore-lining TM1 helix of Orai1, leading to the opening of the channel.
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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.