ArticleScience (New York, N.Y.)2019
Structure and dynamics of the active human parathyroid hormone receptor-1.
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Article in Science (New York, N.Y.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 137 papers.
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137citing papers in PubMed
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137 citing papers in PubMed, 261 citations in OpenAlex.
- Atomic, structural and molecular insights into GPCR ligand binding and signalling.Nature reviews. Molecular cell biology · 2026Review
- Structural basis for small-molecule agonism at GCGR and GIPR via a conserved intracellular allosteric site.Acta pharmacologica Sinica · 2026Article
- Regulation of cAMP levels in osteocytes by mechano-sensitive focal adhesion kinase and phosphodiesterase 8A.iScience · 2026Article
- Molecular basis for cross-activation of NPFF2R by a short PrRP-related peptide.Acta pharmacologica Sinica · 2026Article
- Exploring the conformational landscape of adenylate kinase and beyond with protein folding models.Scientific reports · 2026Article
- Structural basis of PTH1R-β-arrestin core engagement reveals design principles for G-protein-biased therapeutics.Nature structural & molecular biology · 2026Article
- A novel brachydactyly type E syndrome caused by variants in helix 8 of the PTH1R.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2026Article
- Core conformation of arrestin coupling to parathyroid hormone type 1 receptor.Nature communications · 2026Article
- Live-cell imaging reveals decreased cAMP in a PFE-associated c.1050-3C>G PTH1R cell model.Journal of molecular medicine (Berlin, Germany) · 2026Article
- Genetic Determinants of Primary Failure of Eruption: A Comprehensive Review of PTH1R Variants.Genes · 2026Review
- Parathyroid hormone-related protein is a therapeutic target in idiopathic pulmonary fibrosis.Signal transduction and targeted therapy · 2026Article
- Human class B1 GPCR modulation by plasma membrane lipids.Communications biology · 2026Article
- All roads lead to Rome: Emergence of Mechanistic Divergence Shapes Activation of Class B1 G-Protein Coupled Receptors.bioRxiv : the preprint server for biology · 2026Article
- Novel bioactive compounds in the treatment of osteoporosis: chemistry-driven discovery from preclinical validation to clinical translation.Frontiers in chemistry · 2026Review
- Structural and mechanistic insights into dual activation of cagrilintide in amylin and calcitonin receptors.Acta pharmacologica Sinica · 2026Article
- Hypoparathyroidism: a brief historical overview for clinicians.Frontiers in endocrinology · 2026Review
- 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
- Prediction of early biochemical and symptomatic hypocalcemia in thyroid cancer patients after total thyroidectomy.Endocrine · 2025Article
- Advances in Parathyroid Hormone-based medicines.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2025Review
77 more citing papers are in PubMed but not listed here.
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Authors and funding
24 authors at 6 institutions in 2 countries.
Li-Hua Zhao *The CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.ORCID 0000-0002-7175-5174
Shanshan Ma *The CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.ORCID 0000-0003-0626-2645
Ieva Sutkeviciute *Laboratory for GPCR Biology, Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA.ORCID 0000-0002-2168-3344
Dan-Dan Shen *Department of Pathology of Sir Run Run Shaw Hospital and Department of Biophysics, Zhejiang University School of Medicine, Hangzhou 310058, China.ORCID 0000-0001-8757-4602
X Edward ZhouCenter for Cancer and Cell Biology, Innovation and Integration Program, Van Andel Research Institute, Grand Rapids, MI 49503, USA.ORCID 0000-0003-3829-6137
Parker W de WaalCenter for Cancer and Cell Biology, Innovation and Integration Program, Van Andel Research Institute, Grand Rapids, MI 49503, USA.ORCID 0000-0001-6922-9768
Chen-Yao LiThe CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.ORCID 0000-0001-6768-859X
Yanyong KangThe CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Lisa J ClarkLaboratory for GPCR Biology, Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA.ORCID 0000-0003-0484-4596
Frederic G Jean-AlphonseLaboratory for GPCR Biology, Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA.ORCID 0000-0002-7380-5825
Alex D WhiteLaboratory for GPCR Biology, Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA.ORCID 0000-0003-2180-2136
Dehua YangThe CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.ORCID 0000-0003-3028-3243
Antao DaiThe CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.ORCID 0000-0003-4241-5346
Xiaoqing CaiThe CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.ORCID 0000-0002-8995-4518
Jian ChenSchool of Pharmacy, Fudan University, Shanghai 201203, China.ORCID 0000-0001-6363-7752
Cong LiSchool of Pharmacy, Fudan University, Shanghai 201203, China.ORCID 0000-0001-7731-8031
Yi JiangThe CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.ORCID 0000-0002-0723-1413
Tomoyuki WatanabeEndocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Thomas J GardellaEndocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Karsten MelcherCenter for Cancer and Cell Biology, Innovation and Integration Program, Van Andel Research Institute, Grand Rapids, MI 49503, USA.ORCID 0000-0002-9125-4027
Ming-Wei WangThe CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. eric.xu@vai.org mwwang@simm.ac.cn jpv@pitt.edu zhang_yan@zju.edu.cn.ORCID 0000-0001-6550-9017
Jean-Pierre VilardagaLaboratory for GPCR Biology, Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA. eric.xu@vai.org mwwang@simm.ac.cn jpv@pitt.edu zhang_yan@zju.edu.cn.ORCID 0000-0002-1217-1435
H Eric XuThe CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. eric.xu@vai.org mwwang@simm.ac.cn jpv@pitt.edu zhang_yan@zju.edu.cn.ORCID 0000-0002-6829-8144
Yan ZhangDepartment of Pathology of Sir Run Run Shaw Hospital and Department of Biophysics, Zhejiang University School of Medicine, Hangzhou 310058, China. eric.xu@vai.org mwwang@simm.ac.cn jpv@pitt.edu zhang_yan@zju.edu.cn.ORCID 0000-0003-2189-0244
Chinese Academy of Sciences · CNUniversity of Pittsburgh · USVan Andel Institute · USHarvard University · USSir Run Run Shaw Hospital · CNFudan University · CN
Funding
Tissue Phenotyping CoreP01DK011794 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI MANNSTADT, MICHAEL · 1986 to 2023
$44.4MStructure and function of PTH class B GPCRR01DK116780 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Ivet Bahar, Jean-Pierre Vilardaga · 2018 to 2026
$4.2MPTH Inverse Agonists as Therapy for Jansens DiseaseR01DK113039 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI THOMAS J GARDELLA, HARALD W. JUEPPNER · 2018 to 2026
$3.5MPREDOCTORAL TRAINING IN PHARMACOLOGICAL SCIENCEST32GM008424 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI PAGANO, PATRICK J · 1994 to 2019
$3.4MFunctional Polarity of PTH Receptor Signaling: Cellular and Molecular MechanismsR01DK111427 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI FRIEDMAN, PETER A, VILARDAGA, JEAN-PIERRE · 2017 to 2020
$2.4MStructural and Functional Mechanisms of PTH-Receptor SignalingR01DK102495 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CALERO, GUILLERMO ALBERTO, GARDELLA, THOMAS J · 2014 to 2017
$2.0MSustained cAMP Signals Triggered by Internalized PTH Receptor: New Consequences fR01DK087688 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI VILARDAGA, JEAN-PIERRE · 2010 to 2014
$1.6MStructural and Functional Studies of Rhodopsin and G-Protein Coupled Receptor KinasesR01GM127710 · NIGMS · VAN ANDEL RESEARCH INSTITUTE · PI MELCHER, KARSTEN · 2018 to 2020
$1.1MStructural Mechanisms of parathyroid hormone receptor signaling through GsF31AR074843 · NIAMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CLARK, LISA JEAN · 2019 to 2020
$84kNIAMS NIH HHS F31 AR074843NIDDK NIH HHS P01 DK011794NIDDK NIH HHS R01 DK087688NIDDK NIH HHS R01 DK102495NIDDK NIH HHS R01 DK111427NIDDK NIH HHS R01 DK113039NIDDK NIH HHS R01 DK116780NIGMS NIH HHS R01 GM127710NIGMS NIH HHS T32 GM008424
Abstract
The parathyroid hormone receptor-1 (PTH1R) is a class B G protein-coupled receptor central to calcium homeostasis and a therapeutic target for osteoporosis and hypoparathyroidism. Here we report the cryo-electron microscopy structure of human PTH1R bound to a long-acting PTH analog and the stimulatory G protein. The bound peptide adopts an extended helix with its amino terminus inserted deeply into the receptor transmembrane domain (TMD), which leads to partial unwinding of the carboxyl terminus of transmembrane helix 6 and induces a sharp kink at the middle of this helix to allow the receptor to couple with G protein. In contrast to a single TMD structure state, the extracellular domain adopts multiple conformations. These results provide insights into the structural basis and dynamics of PTH binding and receptor activation.
Indexed as
Amino Acid MotifsCryoelectron MicroscopyHumansParathyroid HormoneProtein BindingProtein DomainsReceptor, Parathyroid Hormone, Type 1Parathyroid HormonePTH1R protein, humanReceptor, Parathyroid Hormone, Type 1
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