3c4m

Structure of human parathyroid hormone in complex with the extracellular domain of its G-protein-coupled receptor (PTH1R)

spinqualitylabelsall models 3c4m, resolution 1.95Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3c4m is a 4 chain structure with sequence from Escherichia coli and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.95Å Ligands: GLC, NH2, PRD_900001 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease PTHY_HUMAN Defects in PTH are a cause of familial isolated hypoparathyroidism (FIH) [MIM:146200; also called autosomal dominant hypoparathyroidism or autosomal dominant hypocalcemia. FIH is characterized by hypocalcemia and hyperphosphatemia due to inadequate secretion of parathyroid hormone. Symptoms are seizures, tetany and cramps. FIH exist both as autosomal dominant and recessive forms of hypoparathyroidism. Function PTHY_HUMAN PTH elevates calcium level by dissolving the salts in bone and preventing their renal excretion. Stimulates [1-14C]-2-deoxy-D-glucose (2DG) transport and glycogen synthesis in osteoblastic cells. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Parathyroid hormone (PTH) is central to calcium homeostasis and bone maintenance in vertebrates, and as such it has been used for treating osteoporosis. It acts primarily by binding to its receptor, PTH1R, a member of the class B G protein-coupled receptor (GPCR) family that also includes receptors for glucagon, calcitonin, and other therapeutically important peptide hormones. Despite considerable interest and much research, determining the structure of the receptor-hormone complex has been hindered by difficulties in purifying the receptor and obtaining diffraction-quality crystals. Here, we present a method for expression and purification of the extracellular domain (ECD) of human PTH1R engineered as a maltose-binding protein (MBP) fusion that readily crystallizes. The 1.95-A structure of PTH bound to the MBP-PTH1R-ECD fusion reveals that PTH docks as an amphipathic helix into a central hydrophobic groove formed by a three-layer alpha-beta-betaalpha fold of the PTH1R ECD, resembling a hot dog in a bun. Conservation in the ECD scaffold and the helical structure of peptide hormones emphasizes this hot dog model as a general mechanism of hormone recognition common to class B GPCRs. Our findings reveal critical insights into PTH actions and provide a rational template for drug design that targets this hormone signaling pathway. Molecular recognition of parathyroid hormone by its G protein-coupled receptor.,Pioszak AA, Xu HE Proc Natl Acad Sci U S A. 2008 Apr 1;105(13):5034-9. Epub 2008 Mar 28. PMID:18375760 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA