5FBK
Crystal structure of the extracellular domain of human calcium sensing receptor
Summary for 5FBK
| Entry DOI | 10.2210/pdb5fbk/pdb |
| Related | 5FBH |
| Descriptor | Extracellular calcium-sensing receptor, CYCLOMETHYLTRYPTOPHAN, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total) |
| Functional Keywords | membrane protein, g-protein coupled receptor, ectodomain, signaling protein |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 2 |
| Total formula weight | 131040.57 |
| Authors | Zhang, T.,Zhang, C.,Miller, C.L.,Zou, J.,Moremen, K.W.,Brown, E.M.,Yang, J.J.,Hu, J. (deposition date: 2015-12-14, release date: 2016-06-22, Last modification date: 2020-07-29) |
| Primary citation | Zhang, C.,Zhang, T.,Zou, J.,Miller, C.L.,Gorkhali, R.,Yang, J.Y.,Schilmiller, A.,Wang, S.,Huang, K.,Brown, E.M.,Moremen, K.W.,Hu, J.,Yang, J.J. Structural basis for regulation of human calcium-sensing receptor by magnesium ions and an unexpected tryptophan derivative co-agonist. Sci Adv, 2:e1600241-e1600241, 2016 Cited by PubMed Abstract: 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 Å. 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. PubMed: 27386547DOI: 10.1126/sciadv.1600241 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.1 Å) |
Structure validation
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