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: 7720637
• 负责人: Gary W Daughdrill
• 金额: $ 27.39万
• 依托单位: UNIVERSITY OF IDAHO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-15 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7720637
• 关键词: Biological Models; Classification; Computer Retrieval of Information on Scientific Projects Database; Event; Evolution; Funding; Goals; Grant; Homologous Gene; Human; Institution; Investigation; Maintenance; Natural Selections; Nature; Pattern; Personal Satisfaction; Pliability; Proteins; Research; Research Personnel; Resources; Source; Structure; Tertiary Protein Structure; United States National Institutes of Health; Work; base; chemical property; insertion/deletion mutation; protein structure; replication factor A

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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 该项目的主要目标是通过开发一个更全面的图片，他们的快速相互转换的结构集合，了解进化的限制和模式，管理动态，灵活的蛋白质的自然选择。 为了实现这一目标，我们选择了一个模型系统的基础上，从复制蛋白A（RPA 70）的70 KDa亚基保守的灵活的连接器。 我们正在使用这个模型系统来确定自然选择是否以及如何工作，以保持动态，灵活的蛋白质和蛋白质结构域的结构和功能。 我们已经调查了短暂的二级结构和动态的连接器从四个RPA 70同系物，并观察到在整个进化过程中保持高度动态的字符。 人RPA 70同源物的较大片段揭示了接头末端和侧翼折叠结构域之间的不同相互作用。 我们目前正在研究这是否是一个普遍的特征。 我们还研究了30多个RPA 70同源物的序列保守性，并假设接头是通过插入和缺失事件以及重复扩增而进化的。 最后，贝叶斯分类器正在开发中，以识别动态的，灵活的蛋白质结构的化学性质的基础上。 虽然动态柔性蛋白质和蛋白质结构域在自然界中的存在和重要性是公认的，但这一提议标志着对其进化限制和模式的首次系统性实证研究。