ArticleThe Journal of biological chemistry2007
Identification and dissection of Ca(2+)-binding sites in the extracellular domain of Ca(2+)-sensing receptor.
Article in The Journal of biological chemistry, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 105 citations in OpenAlex.
- A novel missense variant of the calcium-sensing receptor gene associated with familial hypocalciuric hypercalcemia.JBMR plus · 2025Article
- Research progress on cellular behavior of CaSR in cardiovascular diseases.Frontiers in immunology · 2025Review
- Molecular regulation of calcium-sensing receptor (CaSR)-mediated signaling.Chronic diseases and translational medicine · 2024Review
- Mechanism of sensitivity modulation in the calcium-sensing receptor via electrostatic tuning.Nature communications · 2022Article
- Insight into Calcium-Binding Motifs of Intrinsically Disordered Proteins.Biomolecules · 2021Article
- Structural basis for activation and allosteric modulation of full-length calcium-sensing receptor.Science advances · 2021Article
- Review
- 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
- Design and implementation of novel nutraceuticals and derivatives for treating intestinal disorders.Future medicinal chemistry · 2019Review
- The Different Facets of Extracellular Calcium Sensors: Old and New Concepts in Calcium-Sensing Receptor Signalling and Pharmacology.International journal of molecular sciences · 2018Review
- Molecular Basis for Modulation of Metabotropic Glutamate Receptors and Their Drug Actions by Extracellular CaInternational journal of molecular sciences · 2017Review
- Disorders of the calcium-sensing receptor and partner proteins: insights into the molecular basis of calcium homeostasis.Journal of molecular endocrinology · 2016Review
- Structural basis for regulation of human calcium-sensing receptor by magnesium ions and an unexpected tryptophan derivative co-agonist.Science advances · 2016Article
- Pathogenic role of calcium-sensing receptors in the development and progression of pulmonary hypertension.American journal of physiology. Lung cellular and molecular physiology · 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
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Ca(2+)-sensing receptors (CaSRs) represent a class of receptors that respond to changes in the extracellular Ca(2+) concentration ([Ca(2+)](o)) and activate multiple signaling pathways. A major barrier to advancing our understanding of the role of Ca(2+) in regulating CaSRs is the lack of adequate information about their Ca(2+)-binding locations, which is largely hindered by the lack of a solved three-dimensional structure and rapid off rates due to low Ca(2+)-binding affinities. In this paper, we have reported the identification of three potential Ca(2+)-binding sites in a modeled CaSR structure using computational algorithms based on the geometric description and surface electrostatic potentials. Mutation of the predicted ligand residues in the full-length CaSR caused abnormal responses to [Ca(2+)](o), similar to those observed with naturally occurring activating or inactivating mutations of the CaR, supporting the essential role of these predicted Ca(2+)-binding sites in the sensing capability of the CaSR. In addition, to probe the intrinsic Ca(2+)-binding properties of the predicted sequences, we engineered two predicted continuous Ca(2+)-binding sequences individually into a scaffold protein provided by a non-Ca(2+)-binding protein, CD2. We report herein the estimation of the metal-binding affinities of these predicted sites in the CaSR by monitoring aromatic-sensitized Tb(3+) fluorescence energy transfer. Removing the predicted Ca(2+)-binding ligands resulted in the loss of or significantly weakened cation binding. The potential Ca(2+)-binding residues were shown to be involved in Ca(2+)/Ln(3+) binding by high resolution NMR and site-directed mutagenesis, further validating our prediction of Ca(2+)-binding sites within the extracellular domain of the CaSR.
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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.