STRUCTURAL BIOLOGY OF VIRUS ASSEMBLY

病毒组装的结构生物学

• 批准号: 2568186
• 负责人: A C STEVEN
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2568186
• 关键词: bacteriophage T7; bovine papillomavirus; capsid; coliphages; conformation; crosslink; cryoscience; double stranded RNA; hepatitis B virus group; herpes simplex virus 1; image processing; protein biosynthesis; protein structure function; scanning transmission electron microscopy; structural biology; virus DNA; virus RNA; virus assembly; virus protein

This project aims to elucidate the molecular mechanisms that control the assembly of viral capsids, with the ultimate goal of defining prospective targets for antiviral compounds. Over the past year, our most notable technical advance has been achieved in the approximate doubling of the resolution of some three-dimensional density maps calculated from cryo-electron micrographs. Information at the 1 nm level has been derived on bovine papillomavirus in which alfa-helical arms are seen to link neighboring capsomers; and on the hepatitis B virus capsid, which has a high alphalfa- helical content, major elements of secondary structure appear to be directly visible. Large-scale conformational changes have been observed to accompany maturation of the herpesvirus precursor or 'procapsid'. This observation represents yet another developmental feature that HSV shares with the double-stranded DNA-containing bacteriophage paradigm. For a virus of the latter type, coliphage T7, the detailed mode of packing of its genome - a layered spool-like structure - has been determined. In contrast, the double-stranded RNA genome of the fungal virus, L-A, is packed in a markedly different manner, with a predominant spacing of 3.5 - 4.0 nm as compared to 2.6 nm for the DNA viruses. Finally, a second generation phage display system capable of presenting intact domains and proteins of the outer surface of the T4 capsid has been developed and validated.

该项目旨在阐明控制细胞凋亡的分子机制。 病毒衣壳的组装，最终目标是定义预期的 抗病毒化合物的靶点。在过去的一年里，我们最引人注目的 技术进步已经取得了大约一倍， 某些三维密度图的分辨率， 低温电子显微照片在1纳米水平的信息已经得到 在牛乳头瘤病毒中，α-螺旋臂被视为连接 邻近的衣壳上;以及在B型肝炎病毒衣壳上，其具有 高α-螺旋含量，二级结构的主要元素 似乎是直接可见的。大规模的构象变化 观察到伴随疱疹病毒前体的成熟，或 'procapproximate'。这一观察结果代表了另一个发展特征 HSV和含有双链DNA的噬菌体 范例对于后一种类型的病毒，大肠杆菌噬菌体T7， 它的基因组包装--一种分层的线轴状结构--已经被 测定相反，真菌的双链RNA基因组 L-A病毒以明显不同的方式包装，主要是 间距为3.5 - 4.0 nm，而DNA病毒为2.6 nm。 最后，第二代噬菌体展示系统能够呈现 T4衣壳外表面的完整结构域和蛋白质已经被 开发和验证。