ArticleScience advances2016
Structural basis for regulation of human calcium-sensing receptor by magnesium ions and an unexpected tryptophan derivative co-agonist.
Article in Science advances, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 158 citations in OpenAlex.
- Molecular mechanism of p-Coumaric acid in the regulation of AQP2 function through the activation of calcium-sensing receptor signaling.Scientific reports · 2026Article
- Exploring multiple drug actions of a CaNaunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Clinical and Genetic Profile of Chinese Familial Hypocalciuric Hypercalcemia Type 1 (FHH1): A Retrospective Study.Endocrine · 2026Article
- Both calcium-sensing receptor intracellular C-terminal domains support homodimer signaling.Molecular pharmacology · 2025Article
- Magnesium Balance in Chronic Kidney Disease: Mineral Metabolism, Immunosuppressive Therapies and Sodium-Glucose Cotransporter 2 Inhibitors.International journal of molecular sciences · 2025Review
- Article
- Biased agonism of G protein-coupled receptors as a novel strategy for osteoarthritis therapy.Bone research · 2025Review
- Prolonged Diuretic, Natriuretic, and Potassium- and Calcium-Sparing Effect of Hesperidin in Hypertensive Rats.Plants (Basel, Switzerland) · 2025Article
- Cryo-EM structure of the calcium-sensing receptor complexed with the kokumi substance γ-glutamyl-valyl-glycine.Scientific reports · 2025Article
- The Molecular Biology of Placental Transport of Calcium to the Human Foetus.International journal of molecular sciences · 2025Review
- The calcium-sensing receptor: a comprehensive review on its role in calcium homeostasis and therapeutic implications.American journal of translational research · 2025Review
- Research progress on cellular behavior of CaSR in cardiovascular diseases.Frontiers in immunology · 2025Review
- Evolutionary history of calcium-sensing receptors unveils hyper/hypocalcemia-causing mutations.PLoS computational biology · 2024Article
- Ophthalmate is a new regulator of motor functions via CaSR: implications for movement disorders.Brain : a journal of neurology · 2024Article
- Molecular regulation of calcium-sensing receptor (CaSR)-mediated signaling.Chronic diseases and translational medicine · 2024Review
- Glutathione-Based Photoaffinity Probe Identifies Caffeine as a Positive Allosteric Modulator of the Calcium-Sensing Receptor.ACS chemical biology · 2024Article
- Article
- Absence of calcium-sensing receptor basal activity due to inter-subunit disulfide bridges.Communications biology · 2024Article
- Article
- Hyperaminoacidemia induces pancreatic α cell proliferation via synergism between the mTORC1 and CaSR-Gq signaling pathways.Nature communications · 2023Article
13 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
Ca(2+)-sensing receptors (CaSRs) modulate calcium and magnesium homeostasis and many (patho)physiological processes by responding to extracellular stimuli, including divalent cations and amino acids. We report the first crystal structure of the extracellular domain (ECD) of human CaSR bound with Mg(2+) and a tryptophan derivative ligand at 2.1 Å. The structure reveals key determinants for cooperative activation by metal ions and aromatic amino acids. The unexpected tryptophan derivative was bound in the hinge region between two globular ECD subdomains, and represents a novel high-affinity co-agonist of CaSR. The dissection of structure-function relations by mutagenesis, biochemical, and functional studies provides insights into the molecular basis of human diseases arising from CaSR mutations. The data also provide a novel paradigm for understanding the mechanism of CaSR-mediated signaling that is likely shared by the other family C GPCR [G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptor] members and can facilitate the development of novel CaSR-based therapeutics.
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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.