RULES FOR HELIX TERMINATION, THE C CAPPING BOX

螺旋终止规则，C 封盖盒

• 批准号: 2772711
• 负责人: GEORGE I MAKHATADZE
• 金额: $ 13.7万
• 依托单位: TEXAS TECH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-05-01 至 2003-04-20
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2772711
• 关键词: X ray crystallography; fluorescence spectrometry; hydropathy; microcalorimetry; mutant; nuclear magnetic resonance spectroscopy; protein folding; protein sequence; protein structure; stereochemistry; structural biology; thermodynamics; ubiquitin

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.

这个项目的长期目标是从数量上理解 α-螺旋的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作用机制。 折叠，是生物医学研究中最基本的问题之一。这个 这项工作的健康相关意义在于，信息 所获得的结果可用于设计新的蛋白质结构和 提高生物活性蛋白的稳定性。这个 将回答以下问题：1)C封顶中的哪些残留物 Box对于字母螺旋末端的形成很重要 主题？2)不同残基的热力学倾向是什么 在C-盖盒的溶剂外露位置(C2、C1、CCAP和C) 在阿尔法螺旋中，这些倾向与热力学有关吗？ 在其他系统中获得的倾向标度(α-螺旋倾向， β-折叠倾向性)或结构参数(肽骨架 胺氢交换系数、埋藏和裸露表面积等)？ 4)括号疏水相互作用在 字母母题的形成和稳定？这些问题将 通过研究C-帽盒中的特定突变来回答 泛素的α-螺旋结合实验方法， 提供结构(CD、荧光和核磁共振)光谱和 X射线结晶学)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 不同氨基酸残基在不同温度下的能量贡献 C形盖盒的位置。