Hannan, F. M., Kallay, E., Chang, W., Brandi, M. L. & Thakker, R. V. The calcium-sensing receptor in physiology and in calcitropic and noncalcitropic diseases. Nat. Rev. Endocrinol. 15, 33–51 (2018).
Møller, T. C., Moreno-Delgado, D., Pin, J.-P. & Kniazeff, J. Class C G protein-coupled receptors: reviving old couples with new partners. Biophys. Rep. 3, 57–63 (2017).
Conigrave, A. D., Quinn, S. J. & Brown, E. M. l-amino acid sensing by the extracellular Ca2+-sensing receptor. Proc. Natl Acad. Sci. USA 97, 4814–4819 (2000).
Riccardi, D. & Martin, D. The role of the calcium-sensing receptor in the pathophysiology of secondary hyperparathyroidism. NDT Plus 1 (Suppl 1), i7–i11 (2008).
Nemeth, E. F., Van Wagenen, B. C. & Balandrin, M. F. in Progress in Medicinal Chemistry Vol. 57 (eds Witty, D. R. & Cox, B.) 1–86 (Elsevier, 2018).
Geng, Y. et al. Structural mechanism of ligand activation in human calcium-sensing receptor. eLife 5, e13662 (2016).
Zhang, C. et al. Structural basis for regulation of human calcium-sensing receptor by magnesium ions and an unexpected tryptophan derivative co-agonist. Sci. Adv. 2, e1600241 (2016).
Koehl, A. et al. Structural insights into metabotropic glutamate receptor activation. Nature 566, 79–84 (2019).
Fantini, J. & Barrantes, F. J. How cholesterol interacts with membrane proteins: an exploration of cholesterol-binding sites including CRAC, CARC, and tilted domains. Front. Physiol. 4, 31 (2013).
Isberg, V. et al. Generic GPCR residue numbers—aligning topology maps while minding the gaps. Trends Pharmacol. Sci. 36, 22–31 (2015).
Kifor, O., Diaz, R., Butters, R., Kifor, I. & Brown, E. M. The calcium-sensing receptor is localized in caveolin-rich plasma membrane domains of bovine parathyroid cells. J. Biol. Chem. 273, 21708–21713 (1998).
Timmers, H. J. L. M., Karperien, M., Hamdy, N. A., de Boer, H. & Hermus, A. R. M. M. Normalization of serum calcium by cinacalcet in a patient with hypercalcaemia due to a de novo inactivating mutation of the calcium-sensing receptor. J. Intern. Med. 260, 177–182 (2006).
Kunishima, N. et al. Structural basis of glutamate recognition by a dimeric metabotropic glutamate receptor. Nature 407, 971–977 (2000).
Liu, H. et al. Illuminating the allosteric modulation of the calcium-sensing receptor. Proc. Natl Acad. Sci. USA 117, 21711–21722 (2020).
Bushinsky, D. A. et al. One-year safety and efficacy of intravenous etelcalcetide in patients on hemodialysis with secondary hyperparathyroidism. Nephrol. Dial. Transplant. 35, 1769–1778 (2020).
Alexander, S. T. et al. Critical cysteine residues in both the calcium-sensing receptor and the allosteric activator AMG 416 underlie the mechanism of action. Mol. Pharmacol. 88, 853–865 (2015).
Hannan, F. M. et al. Identification of 70 calcium-sensing receptor mutations in hyper- and hypo-calcaemic patients: evidence for clustering of extracellular domain mutations at calcium-binding sites. Hum. Mol. Genet. 21, 2768–2778 (2012).
Robertson, M. J., van Zundert, G. C. P., Borrelli, K. & Skiniotis, G. GemSpot: a pipeline for robust modeling of ligands into cryo-EM maps. Structure 28, 707–716.e3 (2020).
Leach, K. et al. Towards a structural understanding of allosteric drugs at the human calcium-sensing receptor. Cell Res. 26, 574–592 (2016).
Hlavackova, V. et al. Evidence for a single heptahelical domain being turned on upon activation of a dimeric GPCR. EMBO J. 24, 499–509 (2005).
Jacobsen, S. E., Gether, U. & Bräuner-Osborne, H. Investigating the molecular mechanism of positive and negative allosteric modulators in the calcium-sensing receptor dimer. Sci. Rep. 7, 46355 (2017).
Seven, A. B. et al. G protein activation by a metabotropic glutamate receptor. Nature (in the press).
Huang, S. et al. Interdomain movements in metabotropic glutamate receptor activation. Proc. Natl Acad. Sci. USA 108, 15480–15485 (2011).
Ray, K., Fan, G.-F., Goldsmith, P. K. & Spiegel, A. M. The carboxyl terminus of the human calcium receptor. Requirements for cell-surface expression and signal transduction. J. Biol. Chem. 272, 31355–31361 (1997).
Hu, J. et al. A region in the seven-transmembrane domain of the human Ca2+ receptor critical for response to Ca2+. J. Biol. Chem. 280, 5113–5120 (2005).
Shiohara, M. et al. A novel gain-of-function mutation (F821L) in the transmembrane domain of calcium-sensing receptor is a cause of severe sporadic hypoparathyroidism. Eur. J. Pediatr. 163, 94–98 (2004).
Kobilka, B. K. G protein coupled receptor structure and activation. Biochim. Biophys. Acta 1768, 794–807 (2007).
Wu, H. et al. Structure of a class C GPCR metabotropic glutamate receptor 1 bound to an allosteric modulator. Science 344, 58–64 (2014).
Doré, A. S. et al. Structure of class C GPCR metabotropic glutamate receptor 5 transmembrane domain. Nature 511, 557–562 (2014).
Punjani, A., Rubinstein, J. L., Fleet, D. J. & Brubaker, M. A. cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination. Nat. Methods 14, 290–296 (2017).
Punjani, A., Zhang, H. & Fleet, D. J. Non-uniform refinement: adaptive regularization improves single-particle cryo-EM reconstruction. Nat. Methods 17, 1214–1221 (2020).
Punjani, A. & Fleet, D. J. 3D variability analysis: resolving continuous flexibility and discrete heterogeneity from single particle cryo-EM. J. Struct. Biol. 213, 107702 (2021).
Pettersen, E. F. et al. UCSF Chimera–a visualization system for exploratory research and analysis. J. Comput. Chem. 25, 1605–1612 (2004).
Goudet, C. et al. Asymmetric functioning of dimeric metabotropic glutamate receptors disclosed by positive allosteric modulators. J. Biol. Chem. 280, 24380–24385 (2005).
Waterhouse, A. et al. SWISS-MODEL: homology modelling of protein structures and complexes. Nucleic Acids Res. 46 (W1), W296–W303 (2018).
Adams, P. D. et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. D 66, 213–221 (2010).
Emsley, P. & Cowtan, K. Coot: model-building tools for molecular graphics. Acta Crystallogr. D 60, 2126–2132 (2004).
Chen, V. B. et al. MolProbity: all-atom structure validation for macromolecular crystallography. Acta Crystallogr. D 66, 12–21 (2010).
Barad, B. A. et al. EMRinger: side chain-directed model and map validation for 3D cryo-electron microscopy. Nat. Methods 12, 943–946 (2015).
Olsen, R. H. J. et al. TRUPATH, an open-source biosensor platform for interrogating the GPCR transducerome. Nat. Chem. Biol. 16, 841–849 (2020).
Bond, S. R. & Naus, C. C. RF-Cloning.org: an online tool for the design of restriction-free cloning projects. Nucleic Acids Res. 40, W209–W213 (2012).
Papasergi-Scott, M. M. et al. Structures of metabotropic GABAB receptor. Nature 584, 310–314 (2020).
Isberg, V. et al. GPCRdb: an information system for G protein-coupled receptors. Nucleic Acids Res. 44 (D1), D356–D364 (2016).
Crooks, G. E., Hon, G., Chandonia, J. M. & Brenner, S. E. WebLogo: a sequence logo generator. Genome Res. 14, 1188–1190 (2004).