Differential binding of desmopressin and vasopressin to neurophysin-II.
Desmopressin is a synthetic analog of the peptide hormone vasopressin in which the N-terminal alpha-amino group has been removed and L-arginine in position 8 has been replaced by D-arginine. Using 1H-NMR spectroscopy, we show that desmopressin binds to neurophysin-II, whereas deamino-vasopressin does not bind. Thus, the change in configuration at Arg8 causes a significant difference in the binding of these hormones to neurophysin-II. We have determined the structure of desmopressin bound to neurophysin-II using two-dimensional 1H nuclear magnetic resonance-transferred nuclear Overhauser effect techniques. A common binding motif for vasopressin and desmopressin is proposed that includes a positive charge group along with the hydrophobic surface formed by the side chains of Tyr2 and a beta-methylene provided by Phe-3. In vasopressin, the positive charge is provided by the N-terminal NH3+, whereas in desmopressin, the side chain of Arg-8 contributes the positive charge. The type II beta-turn found in residues Cys6-Pro7-D-Arg8-Gly9 of the bound structure of desmopressin folds the Arg8 side chain back toward the disulfide-bond loop, which allows the positive charged side chain of Arg8 to participate in binding. Such a type II beta-turn is not found in deamino-vasopressin in the presence of neurophysin-II.
Wang
J
J
Protein Engineering Network of Centres of Excellence, Department of Biochemistry, University of Alberta, Edmonton, Alberta T6G 2S2, Canada. bds@polaris.biochem.ualberta.ca
Breslow
E
E
Sykes
B D
BD
D000818:Animals; D002417:Cattle; D018360:Crystallography, X-Ray; D003894:Deamino Arginine Vasopressin / Q000737:chemistry / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009481:Neurophysins / Q000378:metabolism*; D010121:Oxytocin / Q000737:chemistry; D011487:Protein Conformation; D014667:Vasopressins / Q000378:metabolism*
D009481:Neurophysins; D014667:Vasopressins; D010121:Oxytocin; D003894:Deamino Arginine Vasopressin