Cryo-EM of Helical Protein and Nucleoprotein Polymers at Near Atomic Resolution

摘要 我们的目标是在拟议的时期内大大扩展我们现有的研究，利用 由于改进了直接电子探测器，电子冷冻显微镜取得了进展， 更好的软件和更快的计算机。这些研究将包括来自 病原菌、交配菌毛、III型和IV型分泌系统以及感染古菌病毒 寄主生活在最极端的环境中。此外，我们还将继续研究小型 分子和多肽自组装成管状和细丝，许多预期 生物医学应用。我们在肌动蛋白方面的工作以及为什么序列如此高度保守 会继续下去。通过研究许多不同的聚合物，我们希望开发出更通用的 可以被其他人应用于生物学中的螺旋聚合物的方法。因为有大量这样的 聚合物存在，从细胞骨架细丝到淀粉样蛋白再到螺旋状病毒(如埃博拉病毒) 这项工作的潜在意义是巨大的，可能会产生很大的影响。

Abstract We aim to greatly extend our existing studies in the proposed period, capitalizing on the great advances in electron cryo-microscopy that have been due to improved direct electron detectors, better software, and faster computers. The studies will include pili and flagellar filaments from pathogenic bacteria, mating pili, type III and IV secretion systems, and archaeal viruses infecting hosts living in the most extreme environments. In addition, we will continue studies of small molecules and peptides that self-assemble into tubes and filaments, many with anticipated biomedical applications. Our work on actin and why the sequence has been so highly conserved will continue. By working on many disparate polymers, we expect to develop more general methods that can be applied by others to helical polymers in biology. Since large numbers of such polymers exist, ranging from cytoskeletal filaments to amyloid to helical viruses (such as Ebola) the potential significance of this work is enormous and likely to have a great impact.