Skaggs School of Pharmacy and Pharmaceutical Sciences, Department of Pharmaceutical Chemistry, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Nucleic Acids Res. 2020 May 21;48(9):5006-5015. doi: 10.1093/nar/gkaa205.
The assembly of double-stranded DNA viruses, from phages to herpesviruses, is strongly conserved. Terminase enzymes processively excise and package monomeric genomes from a concatemeric DNA substrate. The enzymes cycle between a stable maturation complex that introduces site-specific nicks into the duplex and a dynamic motor complex that rapidly translocates DNA into a procapsid shell, fueled by ATP hydrolysis. These tightly coupled reactions are catalyzed by terminase assembled into two functionally distinct nucleoprotein complexes; the maturation complex and the packaging motor complex, respectively. We describe the effects of nucleotides on the assembly of a catalytically competent maturation complex on viral DNA, their effect on maturation complex stability and their requirement for the transition to active packaging motor complex. ATP plays a major role in regulating all of these activities and may serve as a 'nucleotide switch' that mediates transitions between the two complexes during processive genome packaging. These biological processes are recapitulated in all of the dsDNA viruses that package monomeric genomes from concatemeric DNA substrates and the nucleotide switch mechanism may have broad biological implications with respect to virus assembly mechanisms.
双链 DNA 病毒的组装，从噬菌体到疱疹病毒，都具有很强的保守性。端酶酶连续地从连接的 DNA 底物中切割和包装单体基因组。这些酶在稳定的成熟复合物和快速将 DNA 转运到衣壳中的动态马达复合物之间循环，该复合物由 ATP 水解提供动力。这些紧密偶联的反应由组装成两个功能不同的核蛋白复合物的端酶催化：成熟复合物和包装马达复合物。我们描述了核苷酸对病毒 DNA 上催化成熟复合物组装的影响，它们对成熟复合物稳定性的影响，以及它们对向活性包装马达复合物过渡的要求。ATP 在调节所有这些活性中起着主要作用，并且可以作为一种“核苷酸开关”，在连续的基因组包装过程中介导两个复合物之间的转换。这些生物过程在所有从连接的 DNA 底物中包装单体基因组的双链 DNA 病毒中都得到了重现，核苷酸开关机制可能对病毒组装机制具有广泛的生物学意义。
