ArticleNature chemical biology2020
Allosteric interactions in the parathyroid hormone GPCR-arrestin complex formation.
Article in Nature chemical biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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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
30 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Serum parathyroid hormone and risk of sarcopenia: a meta-analysis.Journal of orthopaedic surgery and research · 2025Pooled it
- A Minimalist Model for Navigating Conformational Landscape Uncovers the Activation Mechanism of βACS physical chemistry Au · 2026Article
- Structural basis of PTH1R-β-arrestin core engagement reveals design principles for G-protein-biased therapeutics.Nature structural & molecular biology · 2026Article
- Core conformation of arrestin coupling to parathyroid hormone type 1 receptor.Nature communications · 2026Article
- Structure-Encoded Location Biased Signaling in a Class B GPCR: Focus on the PTH Type 1 Receptor.Handbook of experimental pharmacology · 2026Review
- Insights into G-protein coupling preference from cryo-EM structures of GNature chemical biology · 2025Article
- Allosteric mechanism in the distinctive coupling of GProceedings of the National Academy of Sciences of the United States of America · 2025Article
- DimericeLife · 2025Article
- Genetic Code Expansion: Recent Developments and Emerging Applications.Chemical reviews · 2025Review
- Human diseases caused by homozygous PTH1R mutations.Frontiers in endocrinology · 2025Review
- Fast-diffusing receptor collisions with slow-diffusing peptide ligand assemble the ternary parathyroid hormone-GPCR-arrestin complex.Nature communications · 2024Article
- Noncanonical Amino Acid Tools and Their Application to Membrane Protein Studies.Chemical reviews · 2024Review
- Deciphering the role of glycosaminoglycans in GPCR signaling.Cellular signalling · 2024Review
- Highly biased agonism for GPCR ligands via nanobody tethering.Nature communications · 2024Article
- New Insights into the Structure and Function of Class B1 GPCRs.Endocrine reviews · 2023Article
- Molecular Mechanisms of PTH/PTHrP Class B GPCR Signaling and Pharmacological Implications.Endocrine reviews · 2023Article
- Genetically encoded crosslinkers to address protein-protein interactions.Protein science : a publication of the Protein Society · 2023Review
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- Article
- Altered signaling at the PTH receptor via modified agonist contacts with the extracellular domain provides a path to prolonged agonism in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
Corrections and comments
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Authors and funding
17 authors.
Funding
Abstract
Peptide ligands of class B G-protein-coupled receptors act via a two-step binding process, but the essential mechanisms that link their extracellular binding to intracellular receptor-arrestin interactions are not fully understood. Using NMR, crosslinking coupled to mass spectrometry, signaling experiments and computational approaches on the parathyroid hormone (PTH) type 1 receptor (PTHR), we show that initial binding of the PTH C-terminal part constrains the conformation of the flexible PTH N-terminal signaling epitope before a second binding event occurs. A 'hot-spot' PTH residue, His9, that inserts into the PTHR transmembrane domain at this second step allosterically engages receptor-arrestin coupling. A conformational change in PTHR intracellular loop 3 permits favorable interactions with β-arrestin's finger loop. These results unveil structural determinants for PTHR-arrestin complex formation and reveal that the two-step binding mechanism proceeds via cooperative fluctuations between ligand and receptor, which extend to other class B G-protein-coupled receptors.
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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.