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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。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。列出的机构是 对于中心，这不一定是调查员的机构。 蛋白质伴侣，称为蛋白质二硫化物异构酶（PDI），代表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，并确保正确的二硫键键排列。 尽管它们的重要性，但PDI的作用机理还是很少了解。 已经确定了十多个人类PDI。 有些是特定于折叠某些蛋白质的特异性；其他人似乎是一般行动。 拟议工作的目标之一是了解PDI中底物特异性的起源。 第二个目标是了解涉及二硫键（氧化）及其正确组织（同构）的催化机制。 我们最近确定了特定PDI ERP57的三维结构，该结构参与了主要的组织相容性复合物MHC-I的组装。我们将对不同的PDI进行结构研究，以了解有关其三维形状和功能的更多信息。拟议的研究将有助于我们理解因蛋白质错误折叠而导致的病毒和疾病细胞的进入。