Evidence map›Paper›PMID 26035642›Full record

ArticlePloS one2015

Conformational Changes in the Orai1 C-Terminus Evoked by STIM1 Binding.

Leidamarie Tirado-Lee, Megumi Yamashita, Murali Prakriya

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
4.4field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

30 citing papers in PubMed, 44 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
  5. The Orai Pore Opening Mechanism.International journal of molecular sciences · 2021
    Review
  6. Review
  7. Article
  8. Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. STIM1 activation of Orai1.Cell calcium · 2019
    Review
  14. Stromal-Interacting Molecule 1 (Stim1)/Orai1 Modulates Endothelial Permeability in Ventilator-Induced Lung Injury.Medical science monitor : international medical journal of experimental and clinical research · 2018
    Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Mapping the functional anatomy of Orai1 transmembrane domains for CRAC channel gating.Proceedings of the National Academy of Sciences of the United States of America · 2018
    Article
  20. Distinct gating mechanism of SOC channel involving STIM-Orai coupling and an intramolecular interaction of Orai inProceedings of the National Academy of Sciences of the United States of America · 2018
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

Leidamarie Tirado-LeeDepartment of Pharmacology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States of America.
Megumi YamashitaDepartment of Pharmacology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States of America.
Murali PrakriyaDepartment of Pharmacology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States of America.
Northwestern University · US

Funding

Store-Operated Channels in the Nervous SystemR01NS057499 · NINDS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI PRAKRIYA, MURALI · 2007 to 2022
$5.4M
Activation Mechanisms of Store-Operated Calcium ChannelsR01GM114210 · NIGMS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI PRAKRIYA, MURALI · 2015 to 2018
$1.2M
Store-operated channels in the nervous systemR56NS057499 · NINDS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI PRAKRIYA, MURALI · 2012 to 2012
$344k
NIGMS NIH HHS R01 GM114210NINDS NIH HHS NS057499NINDS NIH HHS R01 NS057499NINDS NIH HHS R56 NS057499
6 · The paper itself

Abstract

Store-operated CRAC channels regulate a wide range of cellular functions including gene expression, chemotaxis, and proliferation. CRAC channels consist of two components: the Orai proteins (Orai1-3), which form the ion-selective pore, and STIM proteins (STIM1-2), which form the endoplasmic reticulum (ER) Ca2+ sensors. Activation of CRAC channels is initiated by the migration of STIM1 to the ER-plasma membrane (PM) junctions, where it directly interacts with Orai1 to open the Ca2+-selective pores of the CRAC channels. The recent elucidation of the Drosophila Orai structure revealed a hexameric channel wherein the C-terminal helices of adjacent Orai subunits associate in an anti-parallel orientation. This association is maintained by hydrophobic interactions between the Drosophila equivalents of human Orai1 residues L273 and L276. Here, we used mutagenesis and chemical cross-linking to assess the nature and extent of conformational changes in the self-associated Orai1 C-termini during STIM1 binding. We find that linking the anti-parallel coiled-coils of the adjacent Orai1 C-termini through disulfide cross-links diminishes STIM1-Orai1 interaction, as assessed by FRET. Conversely, prior binding of STIM1 to the Orai1 C-terminus impairs cross-linking of the Orai1 C-termini. Mutational analysis indicated that a bend of the Orai1 helix located upstream of the self-associated coils (formed by the amino acid sequence SHK) establishes an appropriate orientation of the Orai1 C-termini that is required for STIM1 binding. Together, our results support a model wherein the self-associated Orai1 C-termini rearrange modestly to accommodate STIM1 binding.

Indexed as

Calcium SignalingAmino Acid SequenceAnimalsBinding SitesBlotting, WesternCalcium ChannelsCell MembraneDrosophila ProteinsEndoplasmic ReticulumHEK293 CellsHumansIon Channel GatingMembrane ProteinsMolecular Sequence DataMutagenesis, Site-DirectedMutationCalcium ChannelsDrosophila ProteinsMembrane ProteinsNeoplasm Proteinsolf186-F protein, DrosophilaORAI1 ProteinORAI1 protein, humanProtein SubunitsSTIM1 protein, humanStim protein, DrosophilaStromal Interaction Molecule 1

Identifiers

PMID26035642
PMCPMC4452722
OpenAlexW629042440

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.