Proline-rich Sequences and Polyproline II Helix Formation

富含脯氨酸的序列和聚脯氨酸 II 螺旋的形成

• 批准号: 0110720
• 负责人: Trevor Creamer
• 金额: $ 31.5万
• 依托单位: University of Kentucky Research Foundation
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-15 至 2005-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0110720&HistoricalAwards=false
• 关键词: Proline; rich; Sequences; Polyproline; II

The aim of this project is to determine how proline-rich left-handed polyproline II (PPII) helices form. PPII helices are common in proteins and often play vital roles in critical processes including signal transduction, cell motility, transcription and immune response. PPII helices are involved in both structural roles (e.g., as adopted by collagen) and molecular recognition (e.g., protein-protein interactions mediated by SH3 domains). It is commonly assumed that many proline-rich regions of sequence (PRR's) adopt this confirmation. The goal of this project is to determine the physical basis for PPII helices. This will be achieved via systematic host-guest experiments using a poly(proline)-based host peptide known to form a PPII helix. A combination of experimental and computational methods will be employed. Circular dichroism will be used to measure average PPII helical content of host-guest peptides in order to determine contributions of both individual residues and pairs of residues to the formation of PPII helices. High resolution nuclear magnetic resonance spectroscopy, and molecular dynamics computer simulations will be used to examine the atomic-level interactions that lead to the favoring or disfavoring PPII helix formation. The data obtained from all of these experiments will be combined to form a comprehensive atomic-level picture of PPII helix formation by PRR's. The results of this project will be applicable to studies of a multitude of critical physiological processes ranging from signal transduction to transcription to cell motility. This project lays essential groundwork for future studies of protein-protein interactions involving PPII helices formed by PRR's.

该项目的目的是确定富含脯氨酸的左手聚脯氨酸 II (PPII) 螺旋是如何形成的。 PPII 螺旋在蛋白质中很常见，通常在信号转导、细胞运动、转录和免疫反应等关键过程中发挥重要作用。 PPII 螺旋参与结构作用（例如，胶原蛋白所采用的作用）和分子识别（例如，SH3 结构域介导的蛋白质-蛋白质相互作用）。 人们普遍认为许多富含脯氨酸的序列区域（PRR）都采用了这种确认。 该项目的目标是确定 PPII 螺旋的物理基础。 这将通过使用已知可形成 PPII 螺旋的基于聚脯氨酸的宿主肽进行系统的主客体实验来实现。 将采用实验和计算方法的结合。 圆二色性将用于测量主客体肽的平均 PPII 螺旋含量，以确定单个残基和残基对对 PPII 螺旋形成的贡献。 高分辨率核磁共振波谱和分子动力学计算机模拟将用于检查导致有利或不利 PPII 螺旋形成的原子级相互作用。 从所有这些实验中获得的数据将被组合起来，形成 PRR 形成 PPII 螺旋的全面原子级图像。 该项目的结果将适用于从信号转导到转录到细胞运动等多种关键生理过程的研究。 该项目为未来研究涉及 PRR 形成的 PPII 螺旋的蛋白质-蛋白质相互作用奠定了重要的基础。