ArticleNature communications2020
Structural basis for activation of the growth hormone-releasing hormone receptor.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 82 citations in OpenAlex.
- Structural adaptation associated with signaling preference at the human Growth Hormone-Releasing Hormone Receptor.Protein & cell · 2026Article
- Core conformation of arrestin coupling to parathyroid hormone type 1 receptor.Nature communications · 2026Article
- GHRHR Deficiency Enhances Retinal Ganglion Cell Survival and Visual Functions in Experimental Glaucoma by Inhibiting Ferroptosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Transcriptome and Gene Family Analyses Reveal the Physiological and Immune Regulatory Mechanisms ofAntioxidants (Basel, Switzerland) · 2026Article
- Human class B1 GPCR modulation by plasma membrane lipids.Communications biology · 2026Article
- Therapeutic potential of growth hormone-releasing hormone analogues in cardiovascular and cerebrovascular diseases: mechanisms and preclinical evidence.Frontiers in pharmacology · 2026Review
- The Concise Guide to PHARMACOLOGY 2025/26: G protein-coupled receptors.British journal of pharmacology · 2025Review
- Growth hormone-releasing hormone receptor (GHRH-R) and its signaling.Reviews in endocrine & metabolic disorders · 2025Review
- GHRH and its analogues in central nervous system diseases.Reviews in endocrine & metabolic disorders · 2025Review
- GHRH and the prostate.Reviews in endocrine & metabolic disorders · 2025Review
- Effects of GHRH and its analogues on the Vascular System.Reviews in endocrine & metabolic disorders · 2025Review
- Hypothalamic GHRH.Reviews in endocrine & metabolic disorders · 2025Review
- GHRH in diabetes and metabolism.Reviews in endocrine & metabolic disorders · 2025Review
- Oregano essential oil enhanced body weight and well-being by modulating the HPA axis and 23-nordeoxycholic acid of cecal microbiota in Holstein steers under cold stress.Animal microbiome · 2025Article
- Growth hormone-releasing hormone and its analogues in health and disease.Nature reviews. Endocrinology · 2025Review
- Wellness-enhancing effects of the canine growth hormone releasing hormone therapy mediated by plasmid and electroporation in healthy old dogs.Frontiers in veterinary science · 2025Article
- Microglia-derived ADAM9 promote GHRH neurons pyroptosis by Mad2L2-JNK-caspase-1 pathway in subarachnoid hemorrhage.Journal of neuroinflammation · 2024Article
- Class B1 GPCRs: insights into multireceptor pharmacology for the treatment of metabolic disease.American journal of physiology. Endocrinology and metabolism · 2024Review
- Identification of Small-Molecule Antagonists Targeting the Growth Hormone Releasing Hormone Receptor (GHRHR).Journal of chemical information and modeling · 2024Article
- A Well-Established Gut Microbiota Enhances the Efficiency of Nutrient Metabolism and Improves the Growth Performance ofInternational journal of molecular sciences · 2024Article
Corrections and comments
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Authors and funding
22 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Growth hormone-releasing hormone (GHRH) regulates the secretion of growth hormone that virtually controls metabolism and growth of every tissue through its binding to the cognate receptor (GHRHR). Malfunction in GHRHR signaling is associated with abnormal growth, making GHRHR an attractive therapeutic target against dwarfism (e.g., isolated growth hormone deficiency, IGHD), gigantism, lipodystrophy and certain cancers. Here, we report the cryo-electron microscopy (cryo-EM) structure of the human GHRHR bound to its endogenous ligand and the stimulatory G protein at 2.6 Å. This high-resolution structure reveals a characteristic hormone recognition pattern of GHRH by GHRHR, where the α-helical GHRH forms an extensive and continuous network of interactions involving all the extracellular loops (ECLs), all the transmembrane (TM) helices except TM4, and the extracellular domain (ECD) of GHRHR, especially the N-terminus of GHRH that engages a broad set of specific interactions with the receptor. Mutagenesis and molecular dynamics (MD) simulations uncover detailed mechanisms by which IGHD-causing mutations lead to the impairment of GHRHR function. Our findings provide insights into the molecular basis of peptide recognition and receptor activation, thereby facilitating the development of structure-based drug discovery and precision medicine.
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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.