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.

本项目旨在阐明控制细胞凋亡的分子机制