title: Interaction with model membrane systems induces secondary structure in amino-terminal fragments of parathyroid hormone related protein.
abstract: The secondary structure of amino terminal fragments of human parathyroid hormone related protein (PTHrP) in aqueous solution, in trifluoroethanol solution and in the presence of model membrane systems has been studied by circular dichroism (CD) spectroscopy. Far-UV CD spectra of PTHrP 1-40, 1-34 amide, 7-34 amide and 1-16 are consistent with a predominantly unordered structure. Addition of trifluoroethanol stabilized alpha-helical structure in the 1-34 amide and 7-34 amide peptides. The effect reached a plateau at a trifluoroethanol concentration of approximately 40%, and a helix content of some 23 residues was determined. PTHrP 1-34 amide interacted with palmitoyloleoylphosphatidyl serine vesicles and exhibited an increased alpha-helix content of approximately 12 helical residues. Similar results were observed for monomyristoyllecithin micelles and sodium dodecyl sulfate micelles. No interaction with dimyristoylphosphatidylcholine vesicles was detected by CD. The ability to bind to palmitoyloleoylphosphotidyl serine vesicles was also a feature of the 1-40 and 7-34 fragments, while the 1-16 fragment was apparently unaffected by interaction with this model membrane system. These results indicate that the conformational properties of the functionally significant amino terminal 1-34 region of PTHrP parallel those reported for the corresponding, but largely nonhomologous, region of parathyroid hormone. Conformational similarities may account for the ability of PTHrP to mimic the functional properties of parathyroid hormone.
authors.affiliation: Allelix Biopharmaceuticals Inc., Mississauga, Ontario, Canada.
authors.forename: K J
authors.initials: KJ
authors.lastname: Willis
mesh_terms: D000595:Amino Acid Sequence; D002942:Circular Dichroism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008081:Liposomes / Q000378:metabolism*; D013058:Mass Spectrometry; D008823:Micelles; D008969:Molecular Sequence Data; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D012996:Solutions; D014270:Trifluoroethanol; D014867:Water
chemical_list: D008081:Liposomes; D008823:Micelles; C470121:PTHLH protein, human; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D010743:Phospholipids; D011506:Proteins; D012996:Solutions; D014867:Water; D014270:Trifluoroethanol