ArticleThe Journal of biological chemistry2016
The Activation Mechanism of Glycoprotein Hormone Receptors with Implications in the Cause and Therapy of Endocrine Diseases.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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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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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
25 citing papers in PubMed, 74 citations in OpenAlex.
- Folding, misfolding, and regulation of intracellular traffic of G protein-coupled receptors involved in the hypothalamic-pituitary-gonadal axis.Andrology · 2026Review
- Cryo-electron microscopy for GPCR research and drug discovery in endocrinology and metabolism.Nature reviews. Endocrinology · 2024Review
- Mechanisms of thyrotropin receptor-mediated phenotype variability deciphered by gene mutations and M453T-knockin model.JCI insight · 2024Article
- The relaxin receptor RXFP1 signals through a mechanism of autoinhibition.Nature chemical biology · 2023Article
- Allosteric Regulation of G-Protein-Coupled Receptors: From Diversity of Molecular Mechanisms to Multiple Allosteric Sites and Their Ligands.International journal of molecular sciences · 2023Review
- Structure of full-length TSH receptor in complex with antibody K1-70™.Journal of molecular endocrinology · 2023Article
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- Hinge region mediates signal transmission of luteinizing hormone and chorionic gonadotropin receptor.Computational and structural biotechnology journal · 2022Article
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- Effectiveness Assessment of a Modified Preservation Solution Containing Thyrotropin or Follitropin Based on Biochemical Analysis in Perfundates and Homogenates of Isolated Porcine Kidneys after Static Cold Storage.International journal of molecular sciences · 2021Article
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- Expression and Characterization of Relaxin Family Peptide Receptor 1 Variants.Frontiers in pharmacology · 2021Article
- Modulating TSH Receptor Signaling for Therapeutic Benefit.European thyroid journal · 2020Article
- Glycoprotein G-protein Coupled Receptors in Disease: Luteinizing Hormone Receptors and Follicle Stimulating Hormone Receptors.Diseases (Basel, Switzerland) · 2020Review
- Structural Complexity and Plasticity of Signaling Regulation at the Melanocortin-4 Receptor.International journal of molecular sciences · 2020Review
- FSH for the Treatment of Male Infertility.International journal of molecular sciences · 2020Review
- Ontogeny of the specificity of gonadotropin receptors and gene expression in carp.Endocrine connections · 2019Article
- FSH Beyond Fertility.Frontiers in endocrinology · 2019Review
- Synteny and phylogenetic analysis of paralogous thyrostimulin beta subunits (GpB5) in vertebrates.PloS one · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glycoprotein hormones (GPHs) are the main regulators of the pituitary-thyroid and pituitary-gonadal axes. Selective interaction between GPHs and their cognate G protein-coupled receptors ensure specificity in GPH signaling. The mechanisms of how these hormones activate glycoprotein hormone receptors (GPHRs) or how mutations and autoantibodies can alter receptor function were unclear. Based on the hypothesis that GPHRs contain an internal agonist, we systematically screened peptide libraries derived from the ectodomain for agonistic activity on the receptors. We show that a peptide (p10) derived from a conserved sequence in the C-terminal part of the extracellular N terminus can activate all GPHRs in vitro and in GPHR-expressing tissues. Inactivating mutations in this conserved region or in p10 can inhibit activation of the thyroid-stimulating hormone receptor by autoantibodies. Our data suggest an activation mechanism where, upon extracellular ligand binding, this intramolecular agonist isomerizes and induces structural changes in the 7-transmembrane helix domain, triggering G protein activation. This mechanism can explain the pathophysiology of activating autoantibodies and several mutations causing endocrine dysfunctions such as Graves disease and hypo- and hyperthyroidism. Our findings highlight an evolutionarily conserved activation mechanism of GPHRs and will further promote the development of specific ligands useful to treat Graves disease and other dysfunctions of GPHRs.
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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.