STRUCTURAL STUDIES OF PROTEIN DISULFIDE ISOMERASES

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。 蛋白质伴侣，称为蛋白质二硫键异构酶（PDI），代表了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二硫键的正确排列。 尽管其重要性，PDIs的作用机制知之甚少。 已经确定了十几种人类PDI。 有些是特定的折叠某些蛋白质;其他人似乎是一般的行动。 所提出的工作的目标之一是了解PDIs之间的底物特异性的起源。 第二个目标是了解催化机制，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的PDI，ERp 57，这是参与组装的主要组织相容性复合体MHC-I的三维结构。我们将进行不同的PDI的结构研究，以了解更多关于他们的三维形状和功能。这项拟议中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。

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.