ArticleThe Journal of biological chemistry2009
Molecular determinants of the coupling between STIM1 and Orai channels: differential activation of Orai1-3 channels by a STIM1 coiled-coil mutant.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.
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Who cites it
105 citing papers in PubMed.
- Mechanistic insights into Orai dynamics during pore opening.Channels (Austin, Tex.) · 2026Review
- A supramolecular complex of palmitoylated Orai C-terminal peptide and cyclodextrin targets the plasma membrane to reduce store-operated calcium channel activity.Materials advances · 2026Article
- STIM-Orai signaling in neurons: integrating calcium dynamics and synaptic plasticity.Cell communication and signaling : CCS · 2026Review
- Store-operated calcium entry-based targets for novel cancer therapeutic development.The Journal of pharmacology and experimental therapeutics · 2025Review
- Essential role of N-terminal SAM regions in STIM1 multimerization and function.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- ORAI CaBiomolecules · 2024Review
- Synthetic Biology Meets CaCells · 2024Review
- PGE2 Potentiates Orai1-Mediated Calcium Entry Contributing to Peripheral Sensitization.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Photocrosslinking-induced CRAC channel-like Orai1 activation independent of STIM1.Nature communications · 2023Article
- CRAC and SK Channels: Their Molecular Mechanisms Associated with Cancer Cell Development.Cancers · 2022Review
- ER-resident STIM1/2 couples CaProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Control of STIM and Orai function by post-translational modifications.Cell calcium · 2022Review
- The Role of Lipids in CRAC Channel Function.Biomolecules · 2022Review
- A longer isoform of Stim1 is a negative SOCE regulator but increases cAMP-modulated NFAT signaling.EMBO reports · 2022Article
- Calcium Signals during SARS-CoV-2 Infection: Assessing the Potential of Emerging Therapies.Cells · 2022Review
- Extracellular cysteines C226 and C232 mediate hydrogen sulfide-dependent inhibition of Orai3-mediated store-operated calcium entry.American journal of physiology. Cell physiology · 2022Article
- Orai1 Boosts SK3 Channel Activation.Cancers · 2021Article
- Role of Store-Operated CaBiomolecules · 2021Review
- Role of Orai3 in the Pathophysiology of Cancer.International journal of molecular sciences · 2021Review
- Defects in the STIM1 SOARα2 domain affect multiple steps in the CRAC channel activation cascade.Cellular and molecular life sciences : CMLS · 2021Article
45 more citing papers are in PubMed but not listed here.
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8 authors.
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No grant is acknowledged in the PubMed record.
Abstract
STIM1 and Orai1 have been reported to interact upon store depletion culminating in Ca(2+) release-activated Ca(2+) current activation. Recently, the essential region has been identified within the STIM1 C terminus that includes the second coiled-coil domain C-terminally extended by approximately 50 amino acids and exhibits a strong binding to the Orai1 C terminus. Based on the homology within the Orai family, an analogous scenario might be assumed for Orai2 as well as Orai3 channels as both are activated in a similar STIM1-dependent manner. A combined approach of electrophysiology and Foerster resonance energy transfer microscopy uncovered a general mechanism in the communication of STIM1 with Orai proteins that involved the conserved putative coiled-coil domains in the respective Orai C terminus and the second coiled-coil motif in the STIM1 C terminus. A coiled-coil single mutation in the Orai1 C terminus abrogated communication with the STIM1 C terminus, whereas an analogous mutation in Orai2 and Orai3 still allowed for their moderate activation. However, increasing coiled-coil probability by a gain of function deletion in Orai1 or by generating an Orai1-Orai3 chimera containing the Orai3 C terminus recovered stimulation to a similar extent as with Orai2/3. At the level of STIM1, decreasing probability of the second coiled-coil domain by a single mutation within the STIM1 C terminus abolished activation of Orai1 but still enabled partial stimulation of Orai2/3 channels. A double mutation within the second coiled-coil motif of the STIM1 C terminus fully disrupted communication with all three Orai channels. In aggregate, the impairment in the overall communication between STIM1 and Orai channels upon decreasing probabilities of either one of the putative coiled-coil domains in the C termini might be compatible with the concept of their functional, heteromeric interaction.
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