Salt-dependent structural changes of neurohormones: lithium ions induce conformational rearrangements of ocytocin to a vasopressin-like structure.
The preferred average conformation and structural subdomain interactions of the nonapeptide hormones vasopressin and ocytocin have been analyzed through the determination of their hydrodynamic volume and the thermal coefficient of the frictional resistance to rotation of their tyrosine residue. A spherical gross shape and an ellipsoidal gross shape were assessed respectively for ocytocin and vasopressin by fluorescence polarization analysis. Investigation of the thermal coefficient of viscosity and the critical temperature of both hormones and analogues indicated that strong interactions hold together the two structural subdomains of ocytocin (the flexible six-membered ring and the COOH-terminal tripeptide tail). An opposite situation was found in the case of vasopressin where such interactions could not be detected between the rigid ring and the flexible COOH-terminal tail. Lithium ions were shown to promote ocytocin binding to specific neurophysin sites restricted, under standard conditions, to vasopressin. In the presence of lithium, the gross conformational shape of ocytocin becomes similar to that of vasopressin but in the absence of salt. In addition, the ocytocin ring becomes more rigid in the presence of lithium while decreasing interactions between the ring and the COOH-terminal tail were detected. It is proposed that lithium ions induce specific conformational rearrangements of ocytocin toward a vasopressin-like structure, allowing recognition of this hormonal ligand by a specific vasopressin binding domain of neurophysins.
Rholam
M
M
Nicolas
P
P
Cohen
P
P
D000595:Amino Acid Sequence; D002712:Chlorides / Q000494:pharmacology*; D008094:Lithium / Q000494:pharmacology*; D018021:Lithium Chloride; D009481:Neurophysins / Q000378:metabolism; D010121:Oxytocin / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000378:metabolism; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D014667:Vasopressins / Q000378:metabolism*
D002712:Chlorides; D009481:Neurophysins; D010456:Peptides, Cyclic; D014667:Vasopressins; D010121:Oxytocin; D008094:Lithium; D018021:Lithium Chloride