Evidence map›Paper›PMID 29437838›Full record

ArticleMolecular and cellular biology2018

Probing Dominant Negative Behavior of Glucocorticoid Receptor β through a Hybrid Structural and Biochemical Approach.

Jungki Min, Lalith Perera, Juno M Krahn, Christine M Jewell, Andrea F Moon, John A Cidlowski, Lars C Pedersen

Open access · bronzeAbstract read
In one paragraph

Article in Molecular and cellular biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.9field-weighted citation impact, top 22% 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

9 citing papers in PubMed, 12 citations in OpenAlex.

  1. Review
  2. Review
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  5. Review
  6. Article
  7. Article
  8. Article
  9. Clinical Use and Molecular Action of Corticosteroids in the Pediatric Age.International journal of molecular sciences · 2019
    Review
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 1 institution in 1 country.

Jungki MinGenome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA.
Lalith PereraGenome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA.
Juno M KrahnGenome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA.
Christine M JewellSignal Transduction Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA.
Andrea F MoonGenome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA.
John A CidlowskiSignal Transduction Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA cidlows1@niehs.nih.gov pederse2@niehs.nih.gov.
Lars C PedersenGenome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA cidlows1@niehs.nih.gov pederse2@niehs.nih.gov.ORCID 0000-0002-4488-4077
National Institutes of Health · US

Funding

Glucocorticoid Hormone ActionZIAES090057 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI CIDLOWSKI, JOHN A. · 2009 to 2025
$44.9M
Crystallographic studies of macromolecular structuresZICES102645 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI PEDERSEN, LARS · 2018 to 2025
$12.6M
Crystallographic studies of macromolecular structuresZIAES102645 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI PEDERSEN, LARS · 2009 to 2017
$9.4M
Macromolecular ModelingZICES043010 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI COPELAND, WILLIAM · 2012 to 2025
$5.7M
GLUCOCORTICOID HORMONE ACTIONZ01ES090057 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI CIDLOWSKI, JOHN A. · 1996 to 2008
$4.1M
MACROMOLECULAR MODELING AND CARCINOGENESISZ01ES043010 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI DARDEN, THOMAS A · 1986 to 2008
$1.2M
Intramural NIH HHS Z01 ES043010Intramural NIH HHS Z01 ES090057Intramural NIH HHS ZIA ES102645
6 · The paper itself

Abstract

Glucocorticoid receptor β (GRβ) is associated with glucocorticoid resistance via dominant negative regulation of GRα. To better understand how GRβ functions as a dominant negative inhibitor of GRα at a molecular level, we determined the crystal structure of the ligand binding domain of GRβ complexed with the antagonist RU-486. The structure reveals that GRβ binds RU-486 in the same ligand binding pocket as GRα, and the unique C-terminal amino acids of GRβ are mostly disordered. Binding energy analysis suggests that these C-terminal residues of GRβ do not contribute to RU-486 binding. Intriguingly, the GRβ/RU-486 complex binds corepressor peptide with affinity similar to that of a GRα/RU-486 complex, despite the lack of helix 12. Our biophysical and biochemical analyses reveal that in the presence of RU-486, GRβ is found in a conformation that favors corepressor binding, potentially antagonizing GRα function. This study thus presents an unexpected molecular mechanism by which GRβ could repress transcription.

Indexed as

Amino Acid SequenceEscherichia coliGlucocorticoidsHumansReceptors, Glucocorticoidglucocorticoid receptor alphaglucocorticoid receptor betaGlucocorticoidsReceptors, Glucocorticoiddominant negativeglucocorticoid receptor beta (GRβ)glucocorticoid resistanceRU-486transrepression

Identifiers

PMID29437838
PMCPMC5879464
OpenAlexW2793184777

What OpenQuestion holds

Textmetadata
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.