STRUCTURE DETERMINATION OF RPRP(90 231)

RPRP的结构确定(90 231)

• 批准号: 6220275
• 负责人: HE LIU
• 金额: $ 0.61万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-07-01 至 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6220275
• 关键词: AIDS; biomedical resource; immunology; infection; inflammation; lymphatic system; technology /technique; virus

We have determined the structure of a recombinant fragment (90-231) of Syrian hamster PrP gene product using 3 dimensional heteronuclear NMR. Prions are infectious particles that cause fatal neurodegenerative disorders in humans and animals, such as scrapie in sheep, mad cow disease, and kuru, Cruetzfeld-Jakob, Gerstmann-Staussler-Scheinker disease, and fatal familial insomnia in humans. The diseases' process is unusual in that it is propagated by the change of the conformation of prion proteins from the normal cellular form (PrPc, predominantly alpha helical) to the abnormal aggregated beta-sheet form (PrP Scrapie). The determination of Prp structure is important for both the understanding of prion diseases, and drug design. We use heteronuclear NMR techniques and the graphical NMR software Sparky to make the resonance assignment and NOE cross peak assignment for the determination of the PrP(90-231) structure. The structure was refined using Xplor/Aria and Amber force field. We use molecular graphics (MidasPlus) to check the results of our calculations, and display the NMR constraints with the program noeshow. The interactive process of examining the structure and adding in restraints is heavily dependent on graphics since we have such a great deal of spectral overlap.

我们已经确定了重组片段的结构 (90-231)使用3维的叙利亚仓鼠PrP基因产物 异核核磁共振。 朊病毒是一种传染性颗粒，可导致致命 人类和动物的神经退行性疾病，例如瘙痒病 羊、疯牛病和库鲁病、克鲁茨菲尔德-雅各布病、 Gerstmann-Staussler-Scheinker 病和致命的家族性失眠症 人类。 该疾病的过程很不寻常，因为它是通过以下途径传播的： 朊病毒蛋白构象与正常蛋白相比发生变化 细胞形式（PrPc，主要是α螺旋）异常 聚集的β-片层形式（PrP Scrapie）。 Prp的测定 结构对于理解朊病毒疾病很重要， 和药物设计。 我们使用异核核磁共振技术和 图形 NMR 软件 Sparky 进行共振分配和 NOE 用于确定 PrP(90-231) 的交叉峰分配 结构。 使用 Xplor/Aria 和 Amber Force 改进了结构 场地。 我们使用分子图形（MidasPlus）来检查结果 我们的计算，并用程序显示 NMR 约束 诺秀。 检查结构和结构的交互过程 添加限制很大程度上依赖于图形，因为我们有 如此大量的光谱重叠。