Conformation of a beta-adrenoceptor-derived signal transducing peptide as inferred by circular dichroism and 1H NMR spectroscopy.
The peptide T345-359 representing the fourth intracellular loop of the avian beta-adrenoceptor has been shown to strongly inhibit receptor-mediated adenylate cyclase activity [Münch, G., Dees, C., Hekman, M., & Palm, D. (1991) Eur. J. Biochem. 198, 357-364]. Circular dichroism and two-dimensional 1H NMR techniques were used to investigate the three-dimensional structure of the peptide in trifluoroethanol, phospholipid micelles, and small unilamellar phospholipid vesicles. The prepared vesicles were tested for size distribution and stability by using electron microscopy, photon correlation spectroscopy, and 31P NMR spectroscopy. The peptide T345-359 adopted a predominantly alpha-helical conformation in either trifluoroethanol or phospholipid micelles and vesicles. No structural differences were found for the conformation of the peptide in the presence of phospholipid micelles or vesicles, respectively, using 2D 1H NMR techniques, suggesting a unique conformation of T345-359 when associated with model membranes. A computer-aided model of the micelle-associated peptide was derived. The relevance of the 3D structure of the intracellular loops of receptors to communicate with the G protein in the signal transduction cascade is discussed.
Jung
H
H
Theodor-Boveri-Institut für Biowissenschaften, Universität Würzburg, F.R.G.
Windhaber
R
R
Palm
D
D
Schnackerz
K D
KD
D000595:Amino Acid Sequence; D000818:Animals; D002942:Circular Dichroism; D003198:Computer Simulation; D004912:Erythrocytes / Q000737:chemistry; D036341:Intercellular Signaling Peptides and Proteins; D008081:Liposomes; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000235:genetics; D011487:Protein Conformation; D021382:Protein Sorting Signals / Q000737:chemistry* / Q000235:genetics; D017433:Protein Structure, Secondary; D011943:Receptors, Adrenergic, beta / Q000737:chemistry* / Q000235:genetics; D015398:Signal Transduction; D014422:Turkeys
D036341:Intercellular Signaling Peptides and Proteins; D008081:Liposomes; D008823:Micelles; D010455:Peptides; D021382:Protein Sorting Signals; D011943:Receptors, Adrenergic, beta; C071123:mastoparan X