ArticleThe Journal of biological chemistry2010
Elucidation of a novel extracellular calcium-binding site on metabotropic glutamate receptor 1{alpha} (mGluR1{alpha}) that controls receptor activation.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 32 citations in OpenAlex.
- Molecular regulation of calcium-sensing receptor (CaSR)-mediated signaling.Chronic diseases and translational medicine · 2024Review
- Allosteric modulation of the fish taste receptor type 1 (T1R) family by the extracellular chloride ion.Scientific reports · 2023Article
- The Multiplicity of Infection of Recombinant Vaccinia Virus Expressing the T7 RNA Polymerase Determines the Rescue Efficiency of Vesicular Stomatitis Virus.Frontiers in microbiology · 2022Article
- Structural Mechanism of Cooperative Regulation of Calcium-Sensing Receptor-Mediated Cellular Signaling.Current opinion in physiology · 2020Article
- Design of Calcium-Binding Proteins to Sense Calcium.Molecules (Basel, Switzerland) · 2020Review
- Harnessing Ion-Binding Sites for GPCR Pharmacology.Pharmacological reviews · 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
- Molecular Basis of the Extracellular Ligands Mediated Signaling by the Calcium Sensing Receptor.Frontiers in physiology · 2016Review
- Direct determination of multiple ligand interactions with the extracellular domain of the calcium-sensing receptor.The Journal of biological chemistry · 2014Article
- Identification of an L-phenylalanine binding site enhancing the cooperative responses of the calcium-sensing receptor to calcium.The Journal of biological chemistry · 2014Article
- Extracellular calcium modulates actions of orthosteric and allosteric ligands on metabotropic glutamate receptor 1α.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
- Calciomics: integrative studies of Ca2+-binding proteins and their interactomes in biological systems.Metallomics : integrated biometal science · 2013Review
- Glutamate, glutamate receptors, and downstream signaling pathways.International journal of biological sciences · 2013Review
- Current perspectives on the neurobiology of drug addiction: a focus on genetics and factors regulating gene expression.ISRN neurology · 2012Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Metabotropic glutamate receptor 1α (mGluR1α) exerts important effects on numerous neurological processes. Although mGluR1α is known to respond to extracellular Ca(2+) ([Ca(2+)](o)) and the crystal structures of the extracellular domains (ECDs) of several mGluRs have been determined, the calcium-binding site(s) and structural determinants of Ca(2+)-modulated signaling in the Glu receptor family remain elusive. Here, we identify a novel Ca(2+)-binding site in the mGluR1α ECD using a recently developed computational algorithm. This predicted site (comprising Asp-318, Glu-325, and Asp-322 and the carboxylate side chain of the receptor agonist, Glu) is situated in the hinge region in the ECD of mGluR1α adjacent to the reported Glu-binding site, with Asp-318 involved in both Glu and calcium binding. Mutagenesis studies indicated that binding of Glu and Ca(2+) to their distinct but partially overlapping binding sites synergistically modulated mGluR1α activation of intracellular Ca(2+) ([Ca(2+)](i)) signaling. Mutating the Glu-binding site completely abolished Glu signaling while leaving its Ca(2+)-sensing capability largely intact. Mutating the predicted Ca(2+)-binding residues abolished or significantly reduced the sensitivity of mGluR1α not only to [Ca(2+)](o) and [Gd(3+)](o) but also, in some cases, to Glu. The dual activation of mGluR1α by [Ca(2+)](o) and Glu has important implications for the activation of other mGluR subtypes and related receptors. It also opens up new avenues for developing allosteric modulators of mGluR function that target specific human diseases.
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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.