ArticleNature communications2022
Mechanism of sensitivity modulation in the calcium-sensing receptor via electrostatic tuning.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 17 citations in OpenAlex.
- Ligand-tuned extracellular domain dynamics are correlated with signaling states in an adhesion GPCR.Science advances · 2026Article
- A novel gain-of-function mutation (W818R) of calcium-sensing receptor in a family with autosomal dominant hypocalcemia type 1.Frontiers in endocrinology · 2026Article
- Activation of CaExperimental brain research · 2025Article
- Cryo-EM structure of the calcium-sensing receptor complexed with the kokumi substance γ-glutamyl-valyl-glycine.Scientific reports · 2025Article
- Conformational coupling between extracellular and transmembrane domains modulates holo-adhesion GPCR function.Nature communications · 2024Article
- Differential Behavior of Conformational Dynamics in Active and Inactive States of Cannabinoid Receptor 1.The journal of physical chemistry. B · 2024Article
- Absence of calcium-sensing receptor basal activity due to inter-subunit disulfide bridges.Communications biology · 2024Article
- Article
- Identification and characterization of a novel CASR mutation causing familial hypocalciuric hypercalcemia.Frontiers in endocrinology · 2024Article
- Cholesterol in Class C GPCRs: Role, Relevance, and Localization.Membranes · 2023Article
- Low molecular weight hyaluronan inhibits lung epithelial ion channels by activating the calcium-sensing receptor.Matrix biology : journal of the International Society for Matrix Biology · 2023Article
- Visualizing the Conformational Dynamics of Membrane Receptors Using Single-Molecule FRET.Journal of visualized experiments : JoVE · 2022Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Transfer of information across membranes is fundamental to the function of all organisms and is primarily initiated by transmembrane receptors. For many receptors, how ligand sensitivity is fine-tuned and how disease associated mutations modulate receptor conformation to allosterically affect receptor sensitivity are unknown. Here we map the activation of the calcium-sensing receptor (CaSR) - a dimeric class C G protein-coupled receptor (GPCR) and responsible for maintaining extracellular calcium in vertebrates. We show that CaSR undergoes unique conformational rearrangements compared to other class C GPCRs owing to specific structural features. Moreover, by analyzing disease associated mutations, we uncover a large permissiveness in the architecture of the extracellular domain of CaSR, with dynamics- and not specific receptor topology- determining the effect of a mutation. We show a structural hub at the dimer interface allosterically controls CaSR activation via focused electrostatic repulsion. Changes in the surface charge distribution of this hub, which is highly variable between organisms, finely tune CaSR sensitivity. This is potentially a general tuning mechanism for other dimeric receptors.
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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.