HIGH RESOLUTION STRUCTURE OF HERPESVIRUS

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心机构，不一定为研究者机构。疱疹病毒是人类和动物病毒中最大的家族之一。这些病毒感染可引起多种疾病，包括新生儿播散性疾病、唇疱疹、皮肤病变、单核细胞增多症、成人非流行性脑炎、视网膜炎和癌症。DNA包装是疱疹病毒和许多双链DNA噬菌体复制过程中的关键步骤。DNA包装机器由两个基本组成部分组成：末端酶和门户蛋白。末端酶通过从多联体切割基因组长度的DNA并为包装反应提供能量来催化DNA包装。末端酶包含两个亚基：一个特异性结合病毒多联体DNA的DNA识别亚基，和一个从多联体切割基因组长度DNA的催化亚基。然后通过由环状门户蛋白复合物形成的导管将DNA注射到预先形成的衣壳中，该导管由末端酶的催化亚基提供动力。拟议的研究旨在通过X射线晶体学和cryoEM对HSV-1的末端酶进行高分辨率结构研究。将探索末端酶/门户和衣壳之间的相互作用。这些结构将为控制和预防疱疹病毒引起的感染和疾病的新措施开辟道路。拟议的研究将确定HSV-1末端酶的pUL 15的X射线结构，进行HSV-1衣壳的cryoEM图像重建，研究末端酶、门户复合物和衣壳的组装，并提出HSV-1中DNA包装机制的详细模型。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Herpesvirus is one of the largest families of human and animal viruses. Infection by these viruses can cause a variety of diseases including disseminated disease in the newborn, cold sores, cutaneous lesions, mononucleosis, non-epidemic encephalitis in adults, retinitis, and cancer. DNA packaging is a key step during the replication of herpesvirus and many double-stranded DNA (dsDNA) bacteriophages. The DNA packaging machinery consists of two basic components: a terminase and a portal protein. The terminase catalyzes the DNA packaging by cleaving genome-length DNA from concatemers and providing the energy for the packaging reaction. The terminase contains two subunits: a DNA-recognition subunit that specifically binds to the viral concatemeric DNA, and a catalytic subunit that cleaves the genome-length DNA from the concatemer. The DNA is then injected into a pre-formed capsid through a conduit formed by the ring-like portal protein complex, powered by the catalytic subunit of the terminase. The proposed research is aimed at high resolution structural studies on the terminase of HSV-1 by X-ray crystallography and cryoEM. The interactions between the terminase/portal and the capsid will be explored. The structures will open avenues to novel measures to control and prevent infection and diseases caused by herpesvirus. The proposed research will determine the X-ray structure of pUL15 of the HSV-1 terminase, perform the cryoEM image reconstruction of the HSV-1 capsids, investigate the assembly of the terminase, portal complex, and the capsid, and propose a detailed model for the DNA packaging mechanism in HSV-1.