STRUCTURAL BIOLOGY OF VIRUS ASSEMBLY

该项目旨在阐明控制细胞死亡的分子机制。 病毒衣壳的组装，最终目标是定义 抗病毒化合物的靶标。在过去的一年里，我们最引人注目的是 在技术上取得了进步，大约翻了一番 计算出的某些三维密度图的分辨率 低温电子显微照片。1纳米级别的信息已被推导出来 牛乳头瘤病毒α螺旋臂连接的研究 邻近的衣壳；以及在乙肝病毒衣壳上，它有一个 α-螺旋含量高，二级结构的主要元素 看起来是直接可见的。大规模的构象变化 观察到伴随着疱疹病毒前体或 ‘proapsid’。这一观察代表了另一个发育特征 单纯疱疹病毒与含有双链DNA的噬菌体共有 范例。对于后一种类型的病毒，大肠杆菌T7，详细的模式 其基因组的包装--一种分层的线轴状结构--已经被 下定决心。相比之下，真菌的双链RNA基因组 L-A病毒的包装方式明显不同，主要是一种 间隔3.5-4.0 nm，而DNA病毒的间隔为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被 开发和验证。

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.