Membrane structure of bombesin studied by infrared spectroscopy. Prediction of membrane interactions of gastrin-releasing peptide, neuromedin B, and neuromedin C.
Bombesin, in contact with flat phospholipid bilayer membranes, was shown to adopt a membrane structure similar to that of substance P, dynorphin-(1-13)-tridecapeptide, and adrenocorticotropin-(1-24)-tetracosapeptide. The C-terminal message segment, comprising 8-10 amino acid residues, is inserted into a relatively hydrophobic membrane compartment as an alpha-helical domain oriented perpendicularly on the membrane surface. The N-terminal, hydrophilic tetrapeptide segment remains in the aqueous compartment as a random coil. This was shown with IR and IR attenuated total reflection spectroscopy. Equilibrium thermodynamic estimations confirmed the observed membrane structure with respect to helix length, strength of hydrophobic membrane association, and orientation (caused by favorably oriented molecular amphiphilic and helix electric dipole moments). The membrane structure may explain why Trp-8 and His-12 are essential for biologic activity. Neuromedin B is predicted to be able to adopt a membrane structure similar to that of bombesin. However, gastrin-releasing peptide and neuromedin C are predicted not to behave in the same manner. The molecular mechanism of receptor subtype selection by bombesin-like peptides may prove to be similar to that observed earlier for opioid peptides and the neurokinins.
Department of Molecular Biology and Biophysics, Swiss Federal Institute of Technology (ETH), Zürich.
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D001839:Bombesin; D019886:Gastrin-Releasing Peptide; D006860:Hydrogen Bonding; D008081:Liposomes; D008968:Molecular Conformation; D015287:Neurokinin B / Q000031:analogs & derivatives*; D009479:Neuropeptides; D010446:Peptide Fragments; D010455:Peptides; D010713:Phosphatidylcholines; D013055:Spectrophotometry, Infrared
D008081:Liposomes; D009479:Neuropeptides; D010446:Peptide Fragments; D010455:Peptides; D010713:Phosphatidylcholines; D019886:Gastrin-Releasing Peptide; C040794:neuromedin C; D015287:Neurokinin B; C038393:neuromedin B; D001839:Bombesin; C028694:1-palmitoyl-2-oleoylphosphatidylcholine