ArticlePloS one2012
Extended and structurally supported insights into extracellular hormone binding, signal transduction and organization of the thyrotropin receptor.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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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.
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Who cites it
21 citing papers in PubMed, 54 citations in OpenAlex.
- Article
- Misfolded G Protein-Coupled Receptors and Endocrine Disease. Molecular Mechanisms and Therapeutic Prospects.International journal of molecular sciences · 2021Review
- Modulating TSH Receptor Signaling for Therapeutic Benefit.European thyroid journal · 2020Article
- Structural Complexity and Plasticity of Signaling Regulation at the Melanocortin-4 Receptor.International journal of molecular sciences · 2020Review
- Expression Profiling, Downstream Signaling, and Inter-subunit Interactions of GPA2/GPB5 in the Adult MosquitoFrontiers in endocrinology · 2020Article
- The Pathogenic TSH β-subunit Variant C105Vfs114X Causes a Modified Signaling Profile at TSHR.International journal of molecular sciences · 2019Article
- Editorial: TSH Receptor and Autoimmunity.Frontiers in endocrinology · 2019Article
- Synteny and phylogenetic analysis of paralogous thyrostimulin beta subunits (GpB5) in vertebrates.PloS one · 2019Article
- Antigenic "Hot- Spots" on the TSH Receptor Hinge Region.Frontiers in endocrinology · 2018Article
- Structure-Function Relationships of the Follicle-Stimulating Hormone Receptor.Frontiers in endocrinology · 2018Review
- Structural-Functional Features of the Thyrotropin Receptor: A Class A G-Protein-Coupled Receptor at Work.Frontiers in endocrinology · 2017Review
- Minireview: Insights Into the Structural and Molecular Consequences of the TSH-β Mutation C105Vfs114X.Molecular endocrinology (Baltimore, Md.) · 2016Review
- The Activation Mechanism of Glycoprotein Hormone Receptors with Implications in the Cause and Therapy of Endocrine Diseases.The Journal of biological chemistry · 2016Article
- New small molecule agonists to the thyrotropin receptor.Thyroid : official journal of the American Thyroid Association · 2015Article
- Differences in Signal Activation by LH and hCG are Mediated by the LH/CG Receptor's Extracellular Hinge Region.Frontiers in endocrinology · 2015Article
- A tethered agonist within the ectodomain activates the adhesion G protein-coupled receptors GPR126 and GPR133.Cell reports · 2014Article
- Multiple thyrotropin β-subunit and thyrotropin receptor-related genes arose during vertebrate evolution.PloS one · 2014Article
- Influence of the hinge region and its adjacent domains on binding and signaling patterns of the thyrotropin and follitropin receptor.PloS one · 2014Article
- Allosteric modulators hit the TSH receptor.Endocrinology · 2014Article
- Novel insights on thyroid-stimulating hormone receptor signal transduction.Endocrine reviews · 2013Review
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The hormone thyrotropin (TSH) and its receptor (TSHR) are crucial for the growth and function of the thyroid gland. The TSHR is evolutionary linked with the receptors of follitropin (FSHR) and lutropin/choriogonadotropin (LHR) and their sequences and structures are similar. The extracellular region of TSHR contains more than 350 amino acids and binds hormone and antibodies. Several important questions related to functions and mechanisms of TSHR are still not comprehensively understood. One major reason for these open questions is the lack of any structural information about the extracellular segment of TSHR that connects the N-terminal leucine-rich repeat domain (LRRD) with the transmembrane helix (TMH) 1, the hinge region. It has been shown experimentally that this segment is important for fine tuning of signaling and ligand interactions. A new crystal structure containing most of the extracellular hFSHR region in complex with hFSH has recently been published. Now, we have applied these new structural insights to the homologous TSHR and have generated a structural model of the TSHR LRRD/hinge-region/TSH complex. This structural model is combined and evaluated with experimental data including hormone binding (bTSH, hTSH, thyrostimulin), super-agonistic effects, antibody interactions and signaling regulation. These studies and consideration of significant and non-significant amino acids have led to a new description of mechanisms at the TSHR, including ligand-induced displacements of specific hinge region fragments. This event triggers conformational changes at a convergent center of the LRRD and the hinge region, activating an "intramolecular agonistic unit" close to the transmembrane domain.
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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.