5fbk | pdb_00005fbk

Crystal structure of the extracellular domain of human calcium sensing receptor

spinqualitylabelsall models 5fbk, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5fbk is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.1Å Ligands: BCT, CL, CSO, MG, NAG, TCR Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease CASR_HUMAN Autosomal dominant hypocalcemia;Familial isolated hypoparathyroidism due to impaired PTH secretion;Neonatal severe primary hyperparathyroidism;Familial hypocalciuric hypercalcemia type 1;Bartter syndrome with hypocalcemia. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. Disease susceptibility is associated with variations affecting the gene represented in this entry. Homozygous defects in CASR can be a cause of primary hyperparathyroidism in adulthood. Patients suffer from osteoporosis and renal calculi, have marked hypercalcemia and increased serum PTH concentrations. Function CASR_HUMAN Senses changes in the extracellular concentration of calcium ions. The activity of this receptor is mediated by a G-protein that activates a phosphatidylinositol-calcium second messenger system. Publication Abstract from PubMed Ca(2+)-sensing receptors (CaSRs) modulate calcium and magnesium homeostasis and many (patho)physiological processes by responding to extracellular stimuli, including divalent cations and amino acids. We report the first crystal structure of the extracellular domain (ECD) of human CaSR bound with Mg(2+) and a tryptophan derivative ligand at 2.1 A. The structure reveals key determinants for cooperative activation by metal ions and aromatic amino acids. The unexpected tryptophan derivative was bound in the hinge region between two globular ECD subdomains, and represents a novel high-affinity co-agonist of CaSR. The dissection of structure-function relations by mutagenesis, biochemical, and functional studies provides insights into the molecular basis of human diseases arising from CaSR mutations. The data also provide a novel paradigm for understanding the mechanism of CaSR-mediated signaling that is likely shared by the other family C GPCR [G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptor] members and can facilitate the development of novel CaSR-based therapeutics. Structural basis for regulation of human calcium-sensing receptor by magnesium ions and an unexpected tryptophan derivative co-agonist.,Zhang C, Zhang T, Zou J, Miller CL, Gorkhali R, Yang JY, Schilmiller A, Wang S, Huang K, Brown EM, Moremen KW, Hu J, Yang JJ Sci Adv. 2016 May 27;2(5):e1600241. doi: 10.1126/sciadv.1600241. eCollection 2016, May. PMID:27386547 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA