ArticleeLife2016
Structural mechanism of ligand activation in human calcium-sensing receptor.
Article in eLife, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers, 1 of them a synthesis that pooled it.
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.
The trial behind it
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
124 citing papers in PubMed, 1 synthesis or guideline pooled it, 257 citations in OpenAlex.
- Meta-analysis of the efficacy and safety of sevelamer as hyperphosphatemia therapy for hemodialysis patients.Renal failure · 2023Pooled it
- Anti-CaSR egg yolk antibody improves calcium absorption and bone mineral deposition through intestinal CaSR modulation.Poultry science · 2026Article
- Functional assessment of a constitutively activatingJournal of the Endocrine Society · 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
- Calcium-Sensing Receptor Regulation of Gastrointestinal Hormone Secretion.Endocrine reviews · 2026Review
- A novel homozygous inactivating mutation of the calcium-sensing receptor causing familial hypocalciuric hypercalcemia complicated with primary hyperparathyroidism due to parathyroid adenoma: A case report.The Journal of international medical research · 2026Article
- An atypical venus fly trap domain receptor regulates motility and phagocytosis in the protozoan parasite Entamoeba histolytica.PLoS pathogens · 2026Article
- Calcimimetics and CaSR signaling in CKD-MBD: bone-immune-vascular crosstalk and therapeutic potential.Frontiers in immunology · 2026Review
- Glutathione as a taste modulator: molecular mechanisms of interaction with umami and sweet taste receptors.Food chemistry. Molecular sciences · 2025Article
- Both calcium-sensing receptor intracellular C-terminal domains support homodimer signaling.Molecular pharmacology · 2025Article
- Novel Variants and Clinical Heterogeneity in Pediatric Calcium Metabolism Disorders Identified Through High-Yield Tiered Genetic Testing in a Taiwanese Cohort.Medicina (Kaunas, Lithuania) · 2025Article
- Discovery and mechanistic profiling of novel kokumi peptides from Wuding chicken soup.Food chemistry: X · 2025Article
- Parathyroid glands exhibit reduced parenchymatic chief cells and increased extracellular collagen as a response to a long-term low-phosphorus diet in pigs.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2025Article
- Meaty Aroma Compounds Enhance MSG Umami Perception Through Allosteric Modulation of T1R1/T1R3 Receptor: Evidence from Nasal Clip Sensory Evaluation and Molecular Dynamics Simulation.Foods (Basel, Switzerland) · 2025Article
- Article
- Activation profile of the Atlantic salmon (Salmo salar) calcium-sensing receptor (Casr) by selected L-amino acids.Scientific reports · 2025Article
- Review
- Pathophysiology and therapies of CKD-associated secondary hyperparathyroidism.Clinical kidney journal · 2025Article
- Article
64 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 5 institutions in 3 countries.
Funding
Abstract
Human calcium-sensing receptor (CaSR) is a G-protein-coupled receptor (GPCR) that maintains extracellular Ca(2+) homeostasis through the regulation of parathyroid hormone secretion. It functions as a disulfide-tethered homodimer composed of three main domains, the Venus Flytrap module, cysteine-rich domain, and seven-helix transmembrane region. Here, we present the crystal structures of the entire extracellular domain of CaSR in the resting and active conformations. We provide direct evidence that L-amino acids are agonists of the receptor. In the active structure, L-Trp occupies the orthosteric agonist-binding site at the interdomain cleft and is primarily responsible for inducing extracellular domain closure to initiate receptor activation. Our structures reveal multiple binding sites for Ca(2+) and PO4(3-) ions. Both ions are crucial for structural integrity of the receptor. While Ca(2+) ions stabilize the active state, PO4(3-) ions reinforce the inactive conformation. The activation mechanism of CaSR involves the formation of a novel dimer interface between subunits.
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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.