ArticleScience advances2020
Dynamic allosteric communication pathway directing differential activation of the glucocorticoid receptor.
Article in Science advances, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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.
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.
Who cites it
26 citing papers in PubMed.
- A Molecular-Dynamics-Guided Screening Pipeline Identifies Topical Glucocorticoid Receptor Modulators with Selective Epidermal Activation.Skin pharmacology and physiology · 2026Article
- The Ensemble Basis of Allostery and Function: Insights from Models of Local Unfolding.Journal of molecular biology · 2025Review
- The Evolving Landscape of Protein Allostery: From Computational and Experimental Perspectives.Journal of molecular biology · 2025Review
- From Apo to Ligand-Bound: Unraveling PPARγ-LBD Conformational Shifts via Advanced Molecular Dynamics.ACS omega · 2025Article
- A functional helix shuffled variant of the B domain of Staphylococcus aureus.Protein science : a publication of the Protein Society · 2025Article
- Exploring Binding Sites in Chagas Disease Protein TcP21 Using Integrated Mixed Solvent Molecular Dynamics Approaches.Journal of chemical information and modeling · 2025Article
- Insights into mechanisms of MALT1 allostery from NMR and AlphaFold dynamic analyses.Communications biology · 2024Article
- Modulation of Allostery with Multiple Mechanisms by Hotspot Mutations in TetR.Journal of the American Chemical Society · 2024Article
- Review
- Modulation of Allostery with Multiple Mechanisms by Hotspot Mutations in TetR.bioRxiv : the preprint server for biology · 2023Article
- Protein conformational ensembles in function: roles and mechanisms.RSC chemical biology · 2023Review
- The nuclear receptor LRH-1 discriminates between ligands using distinct allosteric signaling circuits.Protein science : a publication of the Protein Society · 2023Article
- Combining structural and coevolution information to unveil allosteric sites.Chemical science · 2023Article
- Review
- Exploring and Learning the Universe of Protein Allostery Using Artificial Intelligence Augmented Biophysical and Computational Approaches.Journal of chemical information and modeling · 2023Review
- Quaternary glucocorticoid receptor structure highlights allosteric interdomain communication.Nature structural & molecular biology · 2023Article
- Probing conformational landscapes and mechanisms of allosteric communication in the functional states of the ABL kinase domain using multiscale simulations and network-based mutational profiling of allosteric residue potentials.The Journal of chemical physics · 2022Article
- α1-Antitrypsin Binds to the Glucocorticoid Receptor with Anti-Inflammatory and Antimycobacterial Significance in Macrophages.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Design and engineering of allosteric communications in proteins.Current opinion in structural biology · 2022Review
- Cooperativity as quantification and optimization paradigm for nuclear receptor modulators.Chemical science · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Allosteric communication within proteins is a hallmark of biochemical signaling, but the dynamic transmission pathways remain poorly characterized. We combined NMR spectroscopy and surface plasmon resonance to reveal these pathways and quantify their energetics in the glucocorticoid receptor, a transcriptional regulator controlling development, metabolism, and immune response. Our results delineate a dynamic communication network of residues linking the ligand-binding pocket to the activation function-2 interface, where helix 12, a switch for transcriptional activation, exhibits ligand- and coregulator-dependent dynamics coupled to graded activation. The allosteric free energy responds to variations in ligand structure: subtle changes gradually tune allostery while preserving the transmission pathway, whereas substitution of the entire pharmacophore leads to divergent allosteric control by apparently rewiring the communication network. Our results provide key insights that should aid in the design of mechanistically differentiated ligands.
Identifiers
What OpenQuestion holds
Registered trials
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.