The long-term goal of this research is to understand the characteristics of the neurophysin-hormone system through crystallographic studies. Several neurophysindipeptide complexes have been crystallized. They are intact bovine neurophysin II-PHE-TRY-Amide, a modified bovine neurophysin II-PHE-TYR-Amide and a porcine neurophysin I-TYR-PHE-Amide. The peptides are known to bind neurophysins at their hormone binding site. These crystals diffract to beyond 3 angstrom resolution and are suitable for crystallographic studies. We will determine their structures, locate the peptide binding sites and analyze the interactions between the proteins and the peptides. We will also compare the structural details between the internally duplicated segments in neurophysin, and evaluate the magnitude and significance of the duplication in terms of its function. In addition, we will analyze the effect of species-dependent variations in amino-acid sequence on the three-dimensional structure of the neurophysins. Attempts will be made to crystallize other bovine porcine and ovine neurophysins and an oxytocine and/or vassopressin complexes of neurophysin for X-ray diffraction studies.
The aim i s to study the detailed structures of several complexed and uncomplexed neurophysin molecules and to analyze their structural homology and differences. The proposed research could answer many key questions about the structure and function of the neurophysins, such as the cooperative effect in the neurophysin-hormone system, the ligand-induced dimerization, etc. It will also increase our knowledge concerning the molecular basis of the specificity of neurophysin for posterior pituitary hormones, proteinpolypeptide interactions, and protein dynamics in general.
| Rose, J P; Breslow, E; Huang, H B et al. (1991) Crystallographic analysis of the neurophysin-oxytocin complex. A preliminary report. J Mol Biol 221:43-5 |
| Benatan, E; Rose, J; Breslow, E et al. (1991) Crystals of a bovine neurophysin II tripeptide complex. J Mol Biol 222:23-5 |
| Rose, J P; Yang, D; Yoo, C S et al. (1988) Crystals of modified bovine neurophysin II. Eur J Biochem 174:145-7 |
| Wang, B C (1985) Resolution of phase ambiguity in macromolecular crystallography. Methods Enzymol 115:90-112 |
