Structural insights into DNA Topoisomerase II of African Swine Fever Virus

Abstract

AbstractType II topoisomerases are ubiquitous enzymes that play a pivotal role in modulating the topological configuration of dsDNA. These Topo Ⅱ enzymes are indispensable for DNA metabolism and have been extensively investigated in both prokaryotic and eukaryotic organisms. However, understanding of virus-encoded Topo II remains limited. One intriguing example is the African swine fever virus (ASFV), which stands as the sole mammalian-infecting virus encoding a Topo II. In this work, we utilized multiple approaches involving cryo-EM, X-ray crystallography, atomic force microscopy and biochemical assays to investigate the structure and function of ASFV Topo Ⅱ, pP1192R. We determined the structures of pP1192R in different conformational states and confirming its enzymatic activity in vitro. Collectively, our results unveil the basic mechanisms of viral Topo II, thereby not only augmenting our understanding of this kind of intriguing enzymes but also presenting a potential avenue for the intervention strategies to mitigate the impact of African swine fever virus.