CAS Key Laboratory of Infection and Immunity, National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
State Key Laboratory of Biotherapy, West China Hospital, Collaborative Innovation Center for Biotherapy, Sichuan University, Chengdu, 610041, China.
Protein Cell. 2020 May;11(5):339-351. doi: 10.1007/s13238-020-00710-0. Epub 2020 Apr 23.
Genome packaging is a fundamental process in a viral life cycle and a prime target of antiviral drugs. Herpesviruses use an ATP-driven packaging motor/terminase complex to translocate and cleave concatemeric dsDNA into procapsids but its molecular architecture and mechanism are unknown. We report atomic structures of a herpesvirus hexameric terminase complex in both the apo and ADP•BeF3-bound states. Each subunit of the hexameric ring comprises three components-the ATPase/terminase pUL15 and two regulator/fixer proteins, pUL28 and pUL33-unlike bacteriophage terminases. Distal to the nuclease domains, six ATPase domains form a central channel with conserved basic-patches conducive to DNA binding and trans-acting arginine fingers are essential to ATP hydrolysis and sequential DNA translocation. Rearrangement of the nuclease domains mediated by regulatory domains converts DNA translocation mode to cleavage mode. Our structures favor a sequential revolution model for DNA translocation and suggest mechanisms for concerted domain rearrangements leading to DNA cleavage.
基因组包装是病毒生命周期中的一个基本过程，也是抗病毒药物的主要靶点。疱疹病毒使用 ATP 驱动的包装马达/终止酶复合物将连接的 dsDNA 易位并切割成衣壳，但它的分子结构和机制尚不清楚。我们报告了疱疹病毒六聚体终止酶复合物在 apo 和 ADP•BeF3 结合状态下的原子结构。六聚体环的每个亚基由三个组件组成——ATPase/终止酶 pUL15 和两个调节/固定蛋白 pUL28 和 pUL33——与噬菌体终止酶不同。在核酸酶结构域的远端，六个 ATP 酶结构域形成一个中央通道，带有保守的碱性斑点，有利于 DNA 结合，反式作用的精氨酸手指对于 ATP 水解和顺序 DNA 易位是必不可少的。由调节结构域介导的核酸酶结构域的重排将 DNA 易位模式转换为切割模式。我们的结构支持 DNA 易位的顺序旋转模型，并提出了导致 DNA 切割的协同结构域重排的机制。
