Guo Yingying, Yan Renhong
Laboratory of Tropical Veterinary Medicine and Vector Biology, School of Life and Health Sciences, Hainan University, Haikou, China.
Collaborative Innovation Center of One Health, Hainan University, Haikou, China.
FEBS J. 2025 Feb;292(3):510-518. doi: 10.1111/febs.17292. Epub 2024 Oct 29.
The Mpox virus (or Monkeypox virus, MPXV) uses its own encoded proteins to form a replication machine that replicates the viral genome in the host cell cytoplasm, making this machinery a key target for antiviral drug design. The D5 (also known as the OPG117 or E5) protein, a bi-functional helicase-primase enzyme, is crucial in the MPXV replication machinery and genome uncoating process. Recently, cryo-electron microscopy (cryo-EM) structures of D5 in multiple states have been determined. These structures have elucidated the full trajectory of the MPXV D5 helicase-primase as it moves along single-stranded DNA, providing unprecedented advancements in the molecular dynamics and unwinding mechanism. This structural snapshot describes the structural features of the D5 protein and dissects the broader implications of its pivotal role in MPXV replication.
猴痘病毒（或猴天花病毒，MPXV）利用自身编码的蛋白质形成一个复制机器，在宿主细胞质中复制病毒基因组，这使得该机器成为抗病毒药物设计的关键靶点。D5蛋白（也称为OPG117或E5）是一种双功能解旋酶-引发酶，在MPXV复制机器和基因组脱壳过程中至关重要。最近，已确定了多种状态下D5的冷冻电子显微镜（cryo-EM）结构。这些结构阐明了MPXV D5解旋酶-引发酶沿着单链DNA移动时的完整轨迹，在分子动力学和解旋机制方面取得了前所未有的进展。这一结构快照描述了D5蛋白的结构特征，并剖析了其在MPXV复制中关键作用的更广泛影响。
