ArticleMolecular endocrinology (Baltimore, Md.)2014
Identification of a new hormone-binding site on the surface of thyroid hormone receptor.
Article in Molecular endocrinology (Baltimore, Md.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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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.
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Who cites it
16 citing papers in PubMed, 66 citations in OpenAlex.
- In Silico Study of Natural Polyphenols as Potential Metabolic Modulators in Mitigating Lipotoxicity in Non-Alcoholic Fatty Liver Disease via Thyroid Hormone Receptor Alpha Activation.Current issues in molecular biology · 2025Article
- Bile acids target an exposed cavity in the glucocorticoid receptor modulating receptor self-assembly, chromatin binding and transcriptional activity.bioRxiv : the preprint server for biology · 2025Article
- Thyroid hormone receptor beta-2 (TRβ2) overexpression modulates photoreceptor phenotype diversity in a ligand-dependent manner.Frontiers in cell and developmental biology · 2025Article
- Article
- International Union of Basic and Clinical Pharmacology CXIII: Nuclear Receptor Superfamily-Update 2023.Pharmacological reviews · 2023Review
- Exploring Ligand Binding Domain Dynamics in the NRs Superfamily.International journal of molecular sciences · 2022Article
- In vitro and in silico approach to study the hormonal activities of the alternative plasticizer tri-(2-ethylhexyl) trimellitate TEHTM and its metabolites.Archives of toxicology · 2022Article
- Structural overview and perspectives of the nuclear receptors, a major family as the direct targets for small-molecule drugs.Acta biochimica et biophysica Sinica · 2022Article
- A New Mechanism in THRA Resistance: The First Disease-Associated Variant Leading to an Increased Inhibitory Function of THRA2.International journal of molecular sciences · 2021Article
- Molecular modeling and molecular dynamics simulation studies on thyroid hormone receptor from Rattus norvegicus: role of conserved water molecules.Journal of molecular modeling · 2021Article
- Comparative Effects of Di-(2-ethylhexyl)phthalate and Di-(2-ethylhexyl)terephthalate Metabolites on Thyroid Receptors: In Vitro and In Silico Studies.Metabolites · 2021Article
- Echo dephasing and heat capacity from constrained and unconstrained dynamics of triiodothyronine nuclear receptor protein.Journal of biological physics · 2019Article
- Thyroid hormone receptor localization in target tissues.The Journal of endocrinology · 2018Review
- CHARMM Force Field Parameterization of Peroxisome Proliferator-Activated Receptor γ Ligands.International journal of molecular sciences · 2016Article
- Classical nuclear hormone receptor activity as a mediator of complex concentration response relationships for endocrine active compounds.Current opinion in pharmacology · 2014Review
- Structure and function of thyroid hormone plasma membrane transporters.European thyroid journal · 2014Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Thyroid hormone receptors (TRs) are members of the nuclear receptor superfamily of ligand-activated transcription factors involved in cell differentiation, growth, and homeostasis. Although X-ray structures of many nuclear receptor ligand-binding domains (LBDs) reveal that the ligand binds within the hydrophobic core of the ligand-binding pocket, a few studies suggest the possibility of ligands binding to other sites. Here, we report a new x-ray crystallographic structure of TR-LBD that shows a second binding site for T3 and T4 located between H9, H10, and H11 of the TRα LBD surface. Statistical multiple sequence analysis, site-directed mutagenesis, and cell transactivation assays indicate that residues of the second binding site could be important for the TR function. We also conducted molecular dynamics simulations to investigate ligand mobility and ligand-protein interaction for T3 and T4 bound to this new TR surface-binding site. Extensive molecular dynamics simulations designed to compute ligand-protein dissociation constant indicate that the binding affinities to this surface site are of the order of the plasma and intracellular concentrations of the thyroid hormones, suggesting that ligands may bind to this new binding site under physiological conditions. Therefore, the second binding site could be useful as a new target site for drug design and could modulate selectively TR functions.
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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.