STRUCTURAL STUDIES OF PROTEIN DISULFIDE ISOMERASES

蛋白质二硫异构酶的结构研究

• 批准号: 7955545
• 负责人: Kalle B Gehring
• 金额: $ 1.86万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7955545
• 关键词: Cells; Computer Retrieval of Information on Scientific Projects Database; Cysteine; ERp57; Funding; Goals; Grant; Human; Institution; Learning; Major Histocompatibility Complex; Molecular Chaperones; Protein Disulfide Isomerase; Proteins; Research; Research Personnel; Resources; Shapes; Source; Substrate Specificity; United States National Institutes of Health; Virus Diseases; Work; disulfide bond; oxidation; protein folding; protein misfolding; three dimensional structure

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. Protein chaperones, called protein disulfide isomerases (PDI), represent a key step in the folding of proteins. They oxidize cysteine residues in proteins and assure the correct the arrangement of disulfide bonds. In spite of their importance, the mechanism of action of PDIs is poorly understood. More than a dozen human PDIs have been identified. Some are specific for folding certain proteins; others appear to be general in action. One of the goals of the proposed work is to understand the origin of substrate specificity among PDIs. A second goal is to understand the catalytic mechanism which involves both the formation of disulfide bonds (oxidation) and their correct organization (isomeration). We recently determined the three dimensional structure of a specific PDI, ERp57, which is involved in assembly of the major histocompatibility complex MHC-I. We will carry out structural studies of different PDI`s in order to learn more about their three dimensional shape and function. The proposed research will aid our understanding of the entry into the cells of viruses and diseases that result from misfolding of proteins.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 蛋白质伴侣被称为蛋白质二硫键异构酶(PDI)，是蛋白质折叠的关键步骤。它们氧化蛋白质中的半胱氨酸残基，确保二硫键的正确排列。尽管它们很重要，但人们对PDI的作用机制知之甚少。已经确认了十几个人类PDI。有些是特定蛋白质折叠所特有的；另一些似乎是一般作用的。这项拟议工作的目标之一是了解PDI中底物特异性的来源。第二个目标是了解催化机理，包括二硫键的形成(氧化)和它们的正确组织(异构化)。我们最近确定了一个特定PDI的三维结构，ERp57，它参与了主要组织相容性复合体MHC-I的组装。我们将对不同的PDI进行结构研究，以更多地了解它们的三维形状和功能。这项拟议的研究将有助于我们理解蛋白质错误折叠导致的病毒和疾病进入细胞的过程。