STUDY OF NEUROPHYSIN-HORMONE SYSTEMS X-RAY DIFFRACTION

这项研究的长期目标是了解 通过结晶学研究神经生理蛋白-激素系统。几个 神经内科多肽复合体已经结晶。它们完好无损 牛神经物理素Ⅱ-苯丙三胺--一种改良的牛神经物理素类 II-Phe-TYR-酰胺和猪神经物理素I-TYR-Phe-酰胺。这些多肽 已知的是在激素结合部位结合神经内分泌。这些 晶体的衍射分辨率超过3埃，适用于 结晶学研究我们将确定它们的结构，找到 并分析了蛋白质和蛋白质之间的相互作用。 这些多肽。我们还将比较两个版本的结构细节 神经物理蛋白中的内部复制片段，并评估其大小 从功能上讲，复制的意义是什么。此外, 我们将分析氨基酸随物种变化的影响。 神经生理素的三维结构的序列。尝试 将使其他牛、猪和羊的神经内分泌蛋白结晶 神经生理素的催产素和/或加压素复合体的X射线应用 衍射研究。其目的是研究其详细结构。 几种复杂和非复杂的神经物理蛋白分子及其分析 它们在结构上的同源性和差异性。拟议的研究可能 回答有关结构和功能的许多关键问题 神经内分泌激素等在神经内分泌激素中的协同作用 系统，配体诱导的二聚化等。它还将增加我们的 对神经物理素特异性分子基础的认识 对于垂体后叶激素、蛋白多肽相互作用，以及 一般的蛋白质动力学。

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 is 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.