biostudies-literatureUnknown11(5)Hu JIntramural NIH HHSThe human extracellular Ca(2+)-sensing receptor (CaR), a member of the G protein-coupled receptor family 3, plays a key role in the regulation of extracellular calcium homeostasis. It is one of just a few G protein-coupled receptors with a large number of naturally occurring mutations identified in patients. In contrast to the small sizes of its agonists, this large dimeric receptor consists of domains with topologically distinctive orthosteric and allosteric sites. Information derived from studies of naturally occurring mutations, engineered mutations, allosteric modulators and crystal structures of the agonist-binding domain of homologous type 1 metabotropic glutamate receptor and G protein-coupled rhodopsin offers new insights into the structure and function of the CaR.Journal of cellular and molecular medicine908-22https://www.ebi.ac.uk/biostudies/studies/S-EPMC4401263biostudies-literatureStructure and function of the human calcium-sensing receptor: insights from natural and engineered mutations and allosteric modulators.PMC4401263Spiegel AMHu JfalseStructure and function of the human calcium-sensing receptor: insights from natural and engineered mutations and allosteric modulators.The human extracellular Ca(2+)-sensing receptor (CaR), a member of the G protein-coupled receptor family 3, plays a key role in the regulation of extracellular calcium homeostasis. It is one of just a few G protein-coupled receptors with a large number of naturally occurring mutations identified in patients. In contrast to the small sizes of its agonists, this large dimeric receptor consists of domains with topologically distinctive orthosteric and allosteric sites. Information derived from studies of naturally occurring mutations, engineered mutations, allosteric modulators and crystal structures of the agonist-binding domain of homologous type 1 metabotropic glutamate receptor and G protein-coupled rhodopsin offers new insights into the structure and function of the CaR.2007-01-01T00:00:00Z2007 Sep-Oct2025-04-18T16:45:44.013Z2025-04-07T04:08:51.741ZS-EPMC44012631797987310.1111/j.1582-4934.2007.00096.x