RULES FOR HELIX TERMINATION, THE C CAPPING BOX

本项目的长期目标是定量地了解 α-螺旋立体化学和物理化学基础 终止 这意味着更好地理解蛋白质的机制 折叠是生物医学研究中最基本的问题之一。 的 这项工作的健康相关意义在于， 所获得的蛋白质可用于设计新的蛋白质结构， 提高生物活性蛋白质的稳定性。 的 将回答以下问题：1）C-封端中的哪些残基 盒是重要的，为形成的螺旋末端 母题？2)不同残基的热力学倾向是什么 在C-封盖盒的溶剂暴露位置（C2、C1、Ccap和C） 在阿尔法螺旋中3)这些倾向是否与热力学 在其他系统中获得的倾向量表（α-螺旋倾向， β-折叠倾向）或结构参数（肽骨架 酰胺氢交换因子、掩埋和暴露的表面积等）？ 4)什么是包围疏水相互作用， 的形成和稳定性的mesalmotif？这些问题将 可以通过研究在C-加帽盒中的特定突变来回答。 α-螺旋泛素使用的实验方法的组合， 提供结构（CD、荧光和NMR）光谱， X射线晶体学）和热力学（微量热法）信息 在系统上. 根据这些数据，我们将评估结构和 各种氨基酸残基在不同温度下的能量贡献 C-压盖盒的位置。

The long term objective of this project is to understand quantitatively the stereochemical and physico-chemical basis of alpha-helix termination. This means better understanding the mechanism of protein folding, one of the most basic problems in biomedical research. The health-related significance of this work is that the information obtained could be used for the design of new protein structures and the improvement of stabilities of biologically active proteins. The following questions will be answered: 1) Which residues in the C-capping box are important for the formation of the alphal helix termination motif? 2) What are the thermodynamic propensities of different residues at solvent exposed (C2, C1, Ccap & C ) positions of the C-capping box in an alpha-helix? 3) Do these propensities correlate with thermodynamic propensity scales obtained in other systems (alpha-helix propensities, beta-sheet propensities) or structural parameters (peptide backbone amide hydrogen exchange factors, buried and exposed surface area, etc.)? 4) What is the role of the bracketing hydrophobic interactions in formation and stabilization of the alphal motif? These questions will be answered by study of specific mutations in the C-capping box of the alpha-helix of ubiquitin using a combination of experimental methods, providing both structural (CD, fluorescence, and NMR spectroscopies and X-ray crystallography) and thermodynamic (microcalorimetry,) information on the system. From these data, we will evaluate the structural and energetic contributions of various amino acid residues at different positions of C-capping box.