COBRE: UID: PROJ 3: EVOLUTION OF PROTEIN FLEXIBILITY

COBRE：UID：项目 3：蛋白质灵活性的进化

• 批准号: 7381298
• 负责人: Gary W Daughdrill
• 金额: $ 29.11万
• 依托单位: UNIVERSITY OF IDAHO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-02-01 至 2007-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7381298
• 关键词: COBRE; UID; PROJ; EVOLUTION; PROTEIN

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The main goal of this project is to understand the evolutionary constraints and patterns that govern the natural selection of dynamic, flexible proteins by developing a more comprehensive picture of their rapidly interconverting structural ensembles. To accomplish this goal, we have selected a model system based on a conserved flexible linker from the 70 KDa subunit of replication protein A (RPA70). We are using this model system to determine if and how natural selection works to preserve the structure and function of dynamic, flexible proteins and protein domains. We have investigated the transient secondary structure and dynamics of the linkers from four RPA70 homologues and have observed the maintenance of a highly dynamic character throughout the course of evolution. Larger fragments of the human RPA70 homologue have revealed distinct interactions between the ends of the linker and the flanking folded domains. We are currently investigating the whether or not this is a general feature. We have also investigated the sequence conservation of more than 30 RPA70 homologues and hypothesize the linkers are evolving by insertion and deletion events as well as repeat expansion. Finally, Bayesian classifiers are being developed to identify dynamic, flexible protein structures based on chemical properties. While the presence and importance of dynamic flexible proteins and protein domains in nature is well established, this proposal marks the first systematic empirical investigation into their evolutionary constraints and patterns.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构适用于该中心，这不一定是调查员的机构。该项目的主要目的是了解通过对其快速相互互动的结构合奏的更全面的了解来了解动态，灵活蛋白质自然选择的进化约束和模式。为了实现这一目标，我们选择了一个基于70 kDa复制蛋白A（RPA70）的70 kDa亚基的柔性链接器（RPA70）。我们正在使用此模型系统来确定自然选择是否有效地保留动态，柔性蛋白质和蛋白质结构域的结构和功能。我们已经研究了四个RPA70同源物中接头的瞬时二级结构和动力学，并观察到在整个进化过程中维持高度动态的特征。人RPA70同源物的较大片段揭示了连接器的末端与侧翼折叠域之间的不同相互作用。我们目前正在研究这是否是一般功能。我们还研究了30多个RPA70同源物的序列保守性，并假设接头正在通过插入和删除事件以及重复扩展来发展。最后，正在开发贝叶斯分类器，以鉴定基于化学特性的动态，柔性蛋白质结构。虽然自然界中动态柔性蛋白质和蛋白质结构域的存在和重要性已得到充分确立，但该建议标志着对其进化约束和模式的首次系统经验研究。