Comparative study of chicken and human parathyroid hormone-(1-34)-peptides in solution with SDS

Molecular conformations of chicken [cPTH-(1-34)] and human [hPTH-(1-34)] parathyroid hormone fragments in aqueous solutions with various concentrations of SDS were investigated by CD, fluorescence and NMR spectroscopy techniques. In the presence of SDS, chicken and human PTH-(1-34) adopt an a-helical structure making up 32-38% of all the peptide amino acids. The process of the a-helical formation of these two fragments is considerably different. The CD spectral change of hPTH-(1-34) was characteristic of a monotonous increase in the negative peak at 222 nm with increasing SDS concentrations. However, for cPTH-(1-34) a beta-turn is formed first, followed by alpha-helix formation upon an increase in SDS concentrations. The change of the tryptophan fluorescence spectra of cPTH-(1-34) is well correlated with the changes in CD spectra, suggesting that the side chain of Trp23 is involved in the conformational change from random coil to alpha-helix via beta-turn. The three-dimensional structure of cPTH-(1-34) with SDS micelle was elucidated by 1H-NMR at pH 3.8 and 300 K, with the combined use of distance geometry and restrained molecular dynamics calculations. NMR results indicated that it contains two helices encompassing residues 7-12 and 24-30, respectively. The C-terminal helix in the residue range of 24-30 is amphiphilic, which is stabilized by the hydrophobic interactions among Trp23, Leu24 and Lys27.