Evidence map›Paper›PMID 35277487›Full record

ArticleNature communications2022

The structural basis for regulation of the glutathione transporter Ycf1 by regulatory domain phosphorylation.

Nitesh Kumar Khandelwal, Cinthia R Millan, Samantha I Zangari, Samantha Avila, Dewight Williams, Tarjani M Thaker, Thomas M Tomasiak

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
5.1field-weighted citation impact, top 3% 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

24 citing papers in PubMed, 50 citations in OpenAlex.

  1. Article
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  9. The structures of protein kinase A in complex with CFTR: Mechanisms of phosphorylation and noncatalytic activation.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  10. Article
  11. Structural bases for NaNature communications · 2024
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  12. Review
  13. Article
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  15. Article
  16. Broccoli (Frontiers in pharmacology · 2024
    Article
  17. Article
  18. Article
  19. The structure ofProceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  20. 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

7 authors at 3 institutions in 1 country.

Nitesh Kumar KhandelwalDepartment of Chemistry and Biochemistry, University of Arizona, Tucson, AZ, 85721, USA.ORCID http://orcid.org/0000-0002-6319-8048
Cinthia R MillanDepartment of Chemistry and Biochemistry, University of Arizona, Tucson, AZ, 85721, USA.
Samantha I ZangariDepartment of Chemistry and Biochemistry, University of Arizona, Tucson, AZ, 85721, USA.
Samantha AvilaDepartment of Biochemistry and Biophysics, University of California - San Francisco, San Francisco, CA, 94158, USA.ORCID http://orcid.org/0000-0003-1769-9391
Dewight WilliamsEyring Materials Center, Arizona State University, Tempe, AZ, 85287, USA.
Tarjani M ThakerDepartment of Chemistry and Biochemistry, University of Arizona, Tucson, AZ, 85721, USA.
Thomas M TomasiakDepartment of Chemistry and Biochemistry, University of Arizona, Tucson, AZ, 85721, USA. tomasiak@arizona.edu.ORCID http://orcid.org/0000-0002-5884-5968
University of Arizona · USArizona State University · USDuke University · US

Funding

Pacific Northwest Center for Cryo-EM - Screening supplementU24GM129547 · NIGMS · OREGON HEALTH & SCIENCE UNIVERSITY · PI EVANS, JAMES E, GOUAUX, JAMES E · 2018 to 2023
$54.8M
ATP Binding Cassette (ABC) Transporters in Fungal Drug ToleranceR01AI156270 · NIAID · UNIVERSITY OF ARIZONA · PI TOMASIAK, THOMAS MICHAEL · 2021 to 2025
$1.9M
Structural mechanisms for ABC multidrug transporter selectivity and transport ABCR00GM114245 · NIGMS · UNIVERSITY OF ARIZONA · PI TOMASIAK, THOMAS MICHAEL · 2018 to 2020
$746k
JEOL JEM-1400 Transmission Electron MicroscopeS10OD011981 · OD · UNIVERSITY OF ARIZONA · PI ELLIOTT, DAVID A · 2012 to 2012
$365k
NIAID NIH HHS R01 AI156270NIGMS NIH HHS R00 GM114245NIGMS NIH HHS U24 GM129547NIH HHS S10 OD011981
6 · The paper itself

Abstract

Yeast Cadmium Factor 1 (Ycf1) sequesters heavy metals and glutathione into the vacuole to counter cell stress. Ycf1 belongs to the ATP binding cassette C-subfamily (ABCC) of transporters, many of which are regulated by phosphorylation on intrinsically-disordered domains. The regulatory mechanism of phosphorylation is still poorly understood. Here, we report two cryo-EM structures of Ycf1 at 3.4 Å and 4.0 Å resolution in inward-facing open conformations that capture previously unobserved ordered states of the intrinsically disordered regulatory domain (R-domain). R-domain phosphorylation is clearly evident and induces a topology promoting electrostatic and hydrophobic interactions with Nucleotide Binding Domain 1 (NBD1) and the Lasso motif. These interactions stay constant between the structures and are related by rigid body movements of the NBD1/R-domain complex. Biochemical data further show R-domain phosphorylation reorganizes the Ycf1 architecture and is required for maximal ATPase activity. Together, we provide insights into how R-domains control ABCC transporter activity.

Indexed as

ATP-Binding Cassette TransportersSaccharomyces cerevisiae ProteinsCadmiumMembrane Transport ProteinsPhosphorylationSaccharomyces cerevisiaeATP-Binding Cassette TransportersCadmiumglutathione transporterMembrane Transport ProteinsSaccharomyces cerevisiae ProteinsYCF1 protein, S cerevisiae

Identifiers

PMID35277487
PMCPMC8917219
OpenAlexW4221071430

What OpenQuestion holds

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LicenceCC BY
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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.