ArticleBiochemistry2009
Multiple Ca(2+)-binding sites in the extracellular domain of the Ca(2+)-sensing receptor corresponding to cooperative Ca(2+) response.
Article in Biochemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 120 citations in OpenAlex.
- A Multi-Mineral Intervention to Modulate Colonic Mucosal Protein Profile: Results from a 90-Day Trial in Human Subjects.Nutrients · 2021Trial
- Inosine-5'-monophosphate interacts with the TAS1R3 subunit to enhance sweet taste detection.Food chemistry. Molecular sciences · 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
- Identification and characterization of a novel CASR mutation causing familial hypocalciuric hypercalcemia.Frontiers in endocrinology · 2024Article
- Editorial: The role of minerals and trace elements in chronic diseases.Frontiers in cell and developmental biology · 2023Article
- Mechanism of sensitivity modulation in the calcium-sensing receptor via electrostatic tuning.Nature communications · 2022Article
- Liver Protein Expression in NASH Mice on a High-Fat Diet: Response to Multi-Mineral Intervention.Frontiers in nutrition · 2022Article
- Cell-Matrix Interactions Contribute to Barrier Function in Human Colon Organoids.Frontiers in medicine · 2022Article
- Article
- The role of calcium-sensing receptor signaling in regulating transepithelial calcium transport.Experimental biology and medicine (Maywood, N.J.) · 2021Review
- Structural basis for activation and allosteric modulation of full-length calcium-sensing receptor.Science advances · 2021Article
- Therapeutic Opportunities of Targeting Allosteric Binding Sites on the Calcium-Sensing Receptor.ACS pharmacology & translational science · 2021Review
- 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
- Structural Complexity and Plasticity of Signaling Regulation at the Melanocortin-4 Receptor.International journal of molecular sciences · 2020Review
- 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
2 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
6 authors at 3 institutions in 1 country.
Funding
Abstract
A small change in the extracellular Ca(2+) concentration ([Ca(2+)](o)) integrates cell signaling responses in multiple cellular and tissue networks and functions via activation of Ca(2+)-sensing receptors (CaSR). Mainly through binding of Ca(2+) to the large extracellular domain (ECD) of the dimeric CaSR, intracellular Ca(2+) responses are highly cooperative with an apparent Hill coefficient ranging from 2 to 4. We have previously reported the identification of two continuous putative Ca(2+)-binding sites by grafting CaSR-derived, Ca(2+)-binding peptides to a scaffold protein, CD2, that does not bind Ca(2+). In this paper, we predict more potential noncontinuous Ca(2+)-binding sites in the ECD. We dissect the intact CaSR into three globular subdomains, each of which contains two to three predicted Ca(2+)-binding sites. This approach enables us to further understand the mechanisms underlying the binding of multiple metal ions to extended polypeptides derived from a location within the ECD of the CaSR, which would be anticipated to more closely mimic the structure of the native CaSR ECD. Tb(3+) luminescence energy transfer, ANS fluorescence, and NMR studies show biphasic metal-binding components and Ca(2+)-dependent conformational changes in these subdomains. Removing the predicted Ca(2+)-binding ligands in site 1 and site 3 abolishes the first binding step and second binding step, respectively. Studies on these subdomains suggest the existence of multiple metal-binding sites and metal-induced conformational changes that might be responsible for the switching on and off the CaSR by the transition between its open inactive form and closed active form.
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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.