title: Binding specificity of the ectodomain of the parathyroid hormone receptor.
abstract: The parathyroid hormone (PTH)1 receptor is a member of the class B G protein-coupled receptor (GPCR) family and regulates bone and mineral metabolism of vertebrates. A truncated highly active parathyroid hormone fragment PTH (1-34) exerts stimulatory effects on the receptor and is used for treatment of osteoporosis. To study the interacting amino acids of the natural peptide ligand PTH (1-84) with the ectodomain of its receptor we used peptide micro arrays on solid cellulose membranes. The amino acids Arg20 and Trp23 within the identified core binding stretch PTH (20-26) were found to be most important for affinity to the ectodomain of PTH1R. Isothermal titration calorimetry and NMR spectroscopy allowed peptide binding studies in solution and verified peptide positions required for high affinity. With this combination of biochemical and biophysical methods we extend former findings on this essential interaction and can now provide a strategy to screen for optimized therapeutic peptides.
authors.affiliation: Institute of Biochemistry/Biotechnology, Faculty of Science I, Martin-Luther-University Halle-Wittenberg, Germany. nils.drechsler@biochemtech.uni-halle.de
authors.forename: Nils
authors.initials: N
authors.lastname: Drechsler
authors.forename: Julia
authors.initials: J
authors.lastname: Fröbel
authors.forename: Günther
authors.initials: G
authors.lastname: Jahreis
authors.forename: Mohanraj
authors.initials: M
authors.lastname: Gopalswamy
authors.forename: Jochen
authors.initials: J
authors.lastname: Balbach
authors.forename: Eva
authors.initials: E
authors.lastname: Bosse-Doenecke
authors.forename: Rainer
authors.initials: R
authors.lastname: Rudolph
mesh_terms: D000595:Amino Acid Sequence; D002151:Calorimetry; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D044168:Receptor, Parathyroid Hormone, Type 1 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D044168:Receptor, Parathyroid Hormone, Type 1; D011994:Recombinant Proteins