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Structure of human parathyroid hormone 1-37 in solution.

Marx UC, Austermann S, Bayer P, Adermann K, Ejchart A, Sticht H, Walter S, Schmid FX, Jaenicke R, Forssmann WG
J Biol Chem 270 15194-202 (1995)
Cited: 27 times
EuropePMC logo PMID: 7797503

Abstract

Human parathyroid hormone (hPTH), amino acids Ser1 to Leu37, is biologically active with respect to both receptor binding and activation of adenylate cyclase to influence the serum calcium concentration. It induces DNA synthesis via an unknown signal pathway. We investigated the structure of hPTH(1-37) in H2O/buffer solution under near physiological conditions, that is pH 6.0 and 270 mM salt, by circular dichroism, ultracentrifugation, nuclear magnetic resonance spectroscopy, and molecular dynamics calculations. Complete sequence specific assignments of all 1H resonances were performed by using 1H two-dimensional NMR measurements (double quantum-filtered correlated spectroscopy, nuclear Overhauser effect spectroscopy (NOESY), and total correlation spectroscopy with suppression of NOESY-type cross-peaks spectra). hPTH(1-37) obtained helical structure and showed hydrophobic interactions defining a tertiary structure. The NH2-terminal four amino acids of hPTH(1-37) did not show a stable conformation. Evidence for an alpha-helical region between Ile5 and Asn10 was found. This region was followed by a flexible link (Gly12, Lys13) and a well defined turn region, His14 to Ser17. The latter was stabilized by hydrophobic interactions between Trp23 and Leu15. Ser17 through at least Leu28 formed an alpha-helix. Arg20 and Lys27 were involved in the core built by His14 to Ser17. Unrestrained molecular dynamics simulations indicated that the structure was stable on the 200 ps time scale.

Reviews - 1hph mentioned but not cited (1)

  1. International Union of Basic and Clinical Pharmacology. XCIII. The parathyroid hormone receptors--family B G protein-coupled receptors. Gardella TJ, Vilardaga JP. Pharmacol. Rev. 67 310-337 (2015)


Reviews citing this publication (4)

  1. Parathyroid hormone secretion and action: evidence for discrete receptors for the carboxyl-terminal region and related biological actions of carboxyl- terminal ligands. Murray TM, Rao LG, Divieti P, Bringhurst FR. Endocr Rev 26 78-113 (2005)
  2. Molecular properties of the PTH/PTHrP receptor. Gardella TJ, Jüppner H. Trends Endocrinol. Metab. 12 210-217 (2001)
  3. Interaction of PTH and PTHrP with their receptors. Gardella TJ, Jüppner H. Rev Endocr Metab Disord 1 317-329 (2000)
  4. PTH/PTHrP Receptor Signaling, Allostery, and Structures. Sutkeviciute I, Clark LJ, White AD, Gardella TJ, Vilardaga JP. Trends Endocrinol. Metab. 30 860-874 (2019)

Articles citing this publication (22)

  1. Molecular recognition of parathyroid hormone by its G protein-coupled receptor. Pioszak AA, Xu HE. Proc. Natl. Acad. Sci. U.S.A. 105 5034-5039 (2008)
  2. Secondary structure and tertiary fold of the human immunodeficiency virus protein U (Vpu) cytoplasmic domain in solution. Willbold D, Hoffmann S, Rösch P. Eur. J. Biochem. 245 581-588 (1997)
  3. Oral delivery of biologically active parathyroid hormone. Leone-Bay A, Sato M, Paton D, Hunt AH, Sarubbi D, Carozza M, Chou J, McDonough J, Baughman RA. Pharm. Res. 18 964-970 (2001)
  4. Addressing the tertiary structure of human parathyroid hormone-(1-34). Pellegrini M, Royo M, Rosenblatt M, Chorev M, Mierke DF. J. Biol. Chem. 273 10420-10427 (1998)
  5. Parathyroid hormone (PTH)-(1-14) and -(1-11) analogs conformationally constrained by alpha-aminoisobutyric acid mediate full agonist responses via the juxtamembrane region of the PTH-1 receptor. Shimizu N, Guo J, Gardella TJ. J. Biol. Chem. 276 49003-49012 (2001)
  6. Solution structures of human parathyroid hormone fragments hPTH(1-34) and hPTH(1-39) and bovine parathyroid hormone fragment bPTH(1-37). Marx UC, Adermann K, Bayer P, Forssmann WG, Rösch P. Biochem. Biophys. Res. Commun. 267 213-220 (2000)
  7. Purification and characterization of a receptor for human parathyroid hormone and parathyroid hormone-related peptide. Shimada M, Chen X, Cvrk T, Hilfiker H, Parfenova M, Segre GV. J. Biol. Chem. 277 31774-31780 (2002)
  8. NMR structural characterization of HIV-1 virus protein U cytoplasmic domain in the presence of dodecylphosphatidylcholine micelles. Wittlich M, Koenig BW, Stoldt M, Schmidt H, Willbold D. FEBS J. 276 6560-6575 (2009)
  9. Bioactive N-terminal undecapeptides derived from parathyroid hormone: the role of alpha-helicity. Barazza A, Wittelsberger A, Fiori N, Schievano E, Mammi S, Toniolo C, Alexander JM, Rosenblatt M, Peggion E, Chorev M. J. Pept. Res. 65 23-35 (2005)
  10. Structural studies on 26RFa, a novel human RFamide-related peptide with orexigenic activity. Thuau R, Guilhaudis L, Ségalas-Milazzo I, Chartrel N, Oulyadi H, Boivin S, Fournier A, Leprince J, Davoust D, Vaudry H. Peptides 26 779-789 (2005)
  11. The structure of human parathyroid hormone-related protein(1-34) in near-physiological solution. Weidler M, Marx UC, Seidel G, Schäfer W, Hoffmann E, Esswein A, Rösch P. FEBS Lett. 444 239-244 (1999)
  12. An NMR-derived model for the solution structure of oxidized Thermotoga maritima 1[Fe4-S4] ferredoxin. Sticht H, Wildegger G, Bentrop D, Darimont B, Sterner R, Rösch P. Eur. J. Biochem. 237 726-735 (1996)
  13. Backbone dynamics of human parathyroid hormone (1-34): flexibility of the central region under different environmental conditions. Scian M, Marin M, Bellanda M, Tou L, Alexander JM, Rosenblatt M, Chorev M, Peggion E, Mammi S. Biopolymers 84 147-160 (2006)
  14. Conformational and biological characterization of human parathyroid hormone hPTH(1-34) analogues containing beta-amino acid residues in positions 17-19. Schievano E, Mammi S, Carretta E, Fiori N, Corich M, Bisello A, Rosenblatt M, Chorev M, Peggion E. Biopolymers 70 534-547 (2003)
  15. Parathyroid hormone is a heparin/polyanion binding protein: binding energetics and structure modification. Kamerzell TJ, Joshi SB, McClean D, Peplinskie L, Toney K, Papac D, Li M, Middaugh CR. Protein Sci. 16 1193-1203 (2007)
  16. Assessment by 1H NMR spectroscopy of the structural behaviour of human parathyroid-hormone-related protein(1-34) and its close relationship with the N-terminal fragments of human parathyroid hormone in solution. Gronwald W, Schomburg D, Tegge W, Wray V. Biol. Chem. 378 1501-1508 (1997)
  17. Comparative study of chicken and human parathyroid hormone-(1-34)-peptides in solution with SDS. Kanaori K, Takai M, Nosaka AY. Eur. J. Biochem. 249 878-885 (1997)
  18. Concentration-dependent and surface-assisted self-assembly properties of a bioactive estrogen receptor α-derived peptide. Ruggeri FS, Byrne C, Khemtemourian L, Ducouret G, Dietler G, Jacquot Y. J. Pept. Sci. 21 95-104 (2015)
  19. Spectroscopic investigations of HIV-1 trans-activator and related peptides in aqueous solutions. Klostermeier D, Bayer P, Kraft M, Frank RW, Rösch P. Biophys. Chem. 63 87-96 (1997)
  20. Small Molecule Inhibited Parathyroid Hormone Mediated cAMP Response by N-Terminal Peptide Binding. Kumar A, Baumann M, Balbach J. Sci Rep 6 22533 (2016)
  21. Structure of a novel PTH-related peptide hPTH' and its interaction with the PTH receptor. Lin K, Len Y, Feng J, Gao H, You Q, Lin D, Liu J. J. Pept. Sci. 18 413-417 (2012)
  22. NMR structure of a minimum activity domain of human parathyroid peptide hormone: structural origin of receptor activation. Jung J, Lim SK, Kim Y, Lee W. J. Pept. Res. 60 239-246 (2002)


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