FIBER DIFFRACTION FROM MAMMALIAN PRIONS

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。 淀粉样纤维是当正常的可溶性蛋白质改变构象而形成不溶于水的细丝时形成的，这可能会导致严重的损害甚至死亡。淀粉样变性包括阿尔茨海默病、S病、II型糖尿病、遗传性淀粉样变性和多种普恩疾病，包括克雅氏病、疯牛病和瘙痒病。哺乳动物的Prion是由Prion蛋白PrP折叠成异常结构时形成的感染性蛋白质聚集体。淀粉样蛋白？就定义而言？共享交叉测试版结构，但结构细节尚不清楚。淀粉样纤维不能通过结晶学和核磁共振进行表征。纤维衍射是一种确定丝状组件结构细节的有效方法，与电子显微镜相结合为阐明Pron和其他淀粉样蛋白的结构提供了最大的希望。需要结构研究来回答基本的蛋白质折叠问题，了解淀粉样蛋白的形成过程，并进行合理的药物设计。我们使用非常少量的材料，在受控条件下，在强磁场中制作取向溶胶和干燥纤维。磁场已被证明有助于淀粉样蛋白的定向。人工合成的普恩病毒为获取物质开辟了新的可能。Prion可用性的提高，样品制备方法的改进，以及高强度、高质量的同步辐射，共同为获得改进的淀粉样衍射数据提供了前所未有的机会。

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. Amyloid fibers are formed when normally soluble proteins change conformation to form insoluble filaments that can cause severe damage and even death. Amyloidoses include Alzheimer?s disease, type II diabetes, hereditary amyloidoses, and a variety of prion diseases including Creutzfeldt-Jakob disease, BSE (?mad cow disease?), and scrapie. Mammalian prions are infections protein aggregates formed by the prion protein PrP when it folds into aberrant structures. Amyloids ? by definition ? share a cross-beta structure, but the structural details are not known. Amyloid fibers have resisted characterization by crystallography and NMR. Fiber diffraction is an effective method for determining the structural details of filamentous assemblies, and in combination with electron microscopy offers the best hope for elucidating the structures of prions and other amyloids. Structural studies are needed to answer fundamental protein folding questions, to understand the process of amyloid formation, and for rational drug design. We use very small quantities of material to make oriented sols and dried fibers in high magnetic fields under controlled conditions. Magnetic fields have been shown to assist amyloid orientation. Synthetic prions have opened up new possibilities of obtaining material. Improved prion availability, improved methods of specimen preparation, and intense, high quality synchrotron radiation together offer an unprecedented opportunity to obtain improved amyloid diffraction data.