The Mechanism and Regulation of ATP Hydrolysis in a Viral Genome Packaging Motor

项目总结/摘要 许多双链DNA和双链RNA病毒使用一种特殊的酶将它们的基因组包装到预先形成的蛋白质衣壳中。 一种强大的分子机器，被称为病毒包装发动机。一个病毒马达家族，末端酶马达， 与噬菌体和人类病原体有关。Terminase电机有三个组成部分： 将马达的其余部分连接到衣壳的门户，大终止酶（TerL），其具有 马达的活性，以及识别病毒基因组的小终止酶（TerS）。 尽管病毒基因组包装已经研究了30多年，但关于病毒基因组包装的几个问题仍然存在。 运动ATP酶的机制和调节仍然没有答案。填补这些空白对于改善 靶向马达的小分子抑制剂，用于治疗人类病原体，如疱疹病毒。 此外，回答这些问题将改善病毒马达驱动的纳米器件的设计 目前正被开发为基于核酸的治疗递送系统。这些差距并没有被 由于常用的嗜温模型系统的局限性，避免 中温系统的缺点，该项目采用了一种改进的新型嗜热噬菌体 P74-26模型系统。本研究旨在阐明TerL ATP酶活性的机制和调控。 解决目前知识中的这些空白将提供关于病毒马达如何在感染期间转运DNA的见解。 病毒基因组包装。

Project Summary/ Abstract Many dsDNA and dsRNA viruses package their genomes into preformed protein capsids using a powerful molecular machine known as a viral packaging motor. One viral motor family, the terminase motor, is associated with both bacteriophage and human pathogens. Terminase motors have three components: the Portal that connects the rest of the motor to the capsid, the Large Terminase (TerL) which has the enzymatic activity of the motor, and the Small Terminase (TerS), which recognizes the viral genome. Although viral genome packaging has been studied for over 30 years, several questions regarding viral motor ATPase mechanism and regulation remain unanswered. Filling these gaps is critical for improving the small-molecule inhibitors that target the motor for treating human pathogens, such as herpesviruses. Additionally, answering these questions will improve the design of the viral motor-powered nanodevices currently being developed as nucleic acid-based therapeutic delivery systems. These gaps have not been properly addressed due of the limitations of commonly used mesophilic model systems. To avoid the shortcomings of mesophilic systems, this project employs an improved novel thermophilic bacteriophage P74-26 model system. This proposal aims to elucidate the mechanism and regulation of TerL ATPase activity. Addressing these gaps in current knowledge will provide insight as to how viral motors translocate DNA during viral genome packaging.