ArticleThe Journal of biological chemistry2014
Identification of an L-phenylalanine binding site enhancing the cooperative responses of the calcium-sensing receptor to calcium.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Promoting Effects of Urinary Proteins from Stone Formers and Influence of Their Physicochemical Properties on Calcium Oxalate Kidney Stone Formation.Computational and structural biotechnology journal · 2026Article
- 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
- Structural mechanism of cooperative activation of the human calcium-sensing receptor by CaCell research · 2021Article
- Autosomal Dominant Hypocalcemia With Atypical Urine Findings Accompanied by NovelJournal of the Endocrine Society · 2021Article
- Structural Mechanism of Cooperative Regulation of Calcium-Sensing Receptor-Mediated Cellular Signaling.Current opinion in physiology · 2020Article
- Illuminating the allosteric modulation of the calcium-sensing receptor.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- International Union of Basic and Clinical Pharmacology. CVIII. Calcium-Sensing Receptor Nomenclature, Pharmacology, and Function.Pharmacological reviews · 2020Review
- Design of Calcium-Binding Proteins to Sense Calcium.Molecules (Basel, Switzerland) · 2020Review
- G Protein-Coupled Receptors in Taste Physiology and Pharmacology.Frontiers in pharmacology · 2020Review
- The Different Facets of Extracellular Calcium Sensors: Old and New Concepts in Calcium-Sensing Receptor Signalling and Pharmacology.International journal of molecular sciences · 2018Review
- Protein-induced satiation and the calcium-sensing receptor.Diabetes, metabolic syndrome and obesity : targets and therapy · 2018Review
- Article
- Structural basis for regulation of human calcium-sensing receptor by magnesium ions and an unexpected tryptophan derivative co-agonist.Science advances · 2016Article
- Recent advances in understanding the extracellular calcium-sensing receptor.F1000Research · 2016Review
- Molecular Basis of the Extracellular Ligands Mediated Signaling by the Calcium Sensing Receptor.Frontiers in physiology · 2016Review
- Intracellular Ca(2+) oscillations generated via the extracellular Ca(2+)-sensing receptor (CaSR) in response to extracellular Ca(2+) or L-phenylalanine: Impact of the highly conservative mutation Ser170Thr.Biochemical and biophysical research communications · 2015Article
- Direct determination of multiple ligand interactions with the extracellular domain of the calcium-sensing receptor.The Journal of biological chemistry · 2014Article
- Role of Ca2+ and L-Phe in regulating functional cooperativity of disease-associated "toggle" calcium-sensing receptor mutations.PloS one · 2014Article
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
Functional positive cooperative activation of the extracellular calcium ([Ca(2+)]o)-sensing receptor (CaSR), a member of the family C G protein-coupled receptors, by [Ca(2+)]o or amino acids elicits intracellular Ca(2+) ([Ca(2+)]i) oscillations. Here, we report the central role of predicted Ca(2+)-binding site 1 within the hinge region of the extracellular domain (ECD) of CaSR and its interaction with other Ca(2+)-binding sites within the ECD in tuning functional positive homotropic cooperativity caused by changes in [Ca(2+)]o. Next, we identify an adjacent L-Phe-binding pocket that is responsible for positive heterotropic cooperativity between [Ca(2+)]o and L-Phe in eliciting CaSR-mediated [Ca(2+)]i oscillations. The heterocommunication between Ca(2+) and an amino acid globally enhances functional positive homotropic cooperative activation of CaSR in response to [Ca(2+)]o signaling by positively impacting multiple [Ca(2+)]o-binding sites within the ECD. Elucidation of the underlying mechanism provides important insights into the longstanding question of how the receptor transduces signals initiated by [Ca(2+)]o and amino acids into intracellular signaling events.
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