Conformation and self-association of the peptide hormone substance P: Fourier-transform infrared spectroscopic study.
Fourier-transform i.r. (f.t.i.r.) spectroscopy has been applied to the study of the conformational properties of substance P in aqueous solution. Spectra were obtained in the presence of lipid membranes and Ca2+ to assess the role of these factors in induction of the active conformation of the peptide. In aqueous solution substance P was found to be predominantly unstructured at physiological p2H, where the lack of long-range order is probably related to charge repulsion along the peptide chain. However, substance P aggregated in aqueous solution at p2H > 10.0. Little or no induction of secondary structure was seen on addition of the peptide to negatively charged bilayers, suggesting that interaction with a membrane surface does not play an important role in the stabilization of the active conformation of the peptide. In fact, substance P was found to aggregate in the presence of charged lipids, which would tend to hinder rather than enhance interaction with the receptor. We propose a model for the aggregation of substance P at the bilayer surface, based on our studies of the effect of p2H and lipid/peptide ratio on spectra. Addition of Ca2+ had no effect upon the secondary structure of the peptide or on its interactions with membranes.
Choo
L P
LP
Institute for Biodiagnostics, National Research Council of Canada, Winnipeg, Manitoba.
Jackson
M
M
Mantsch
H H
HH
D000595:Amino Acid Sequence; D002118:Calcium / Q000494:pharmacology; D004563:Electrochemistry; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D008563:Membrane Lipids / Q000494:pharmacology; D008969:Molecular Sequence Data; D010743:Phospholipids / Q000494:pharmacology; D011487:Protein Conformation / Q000187:drug effects; D017433:Protein Structure, Secondary; D017550:Spectroscopy, Fourier Transform Infrared; D013373:Substance P / Q000737:chemistry*
D008563:Membrane Lipids; D010743:Phospholipids; D013373:Substance P; D002118:Calcium