Department of Molecular Biosciences, Northwestern University, Evanston, United States.
Elife. 2022 Aug 15;11:e72702. doi: 10.7554/eLife.72702.
Topoisomerase V is a unique topoisomerase that combines DNA repair and topoisomerase activities. The enzyme has an unusual arrangement, with a small topoisomerase domain followed by 12 tandem (HhH) domains, which include 3 AP lyase repair domains. The uncommon architecture of this enzyme bears no resemblance to any other known topoisomerase. Here, we present structures of topoisomerase V in complex with DNA. The structures show that the (HhH) domains wrap around the DNA and in this manner appear to act as a processivity factor. There is a conformational change in the protein to expose the topoisomerase active site. The DNA bends sharply to enter the active site, which melts the DNA and probably facilitates relaxation. The structures show a DNA-binding mode not observed before and provide information on the way this atypical topoisomerase relaxes DNA. In common with type IB enzymes, topoisomerase V relaxes DNA using a controlled rotation mechanism, but the structures show that topoisomerase V accomplishes this in different manner. Overall, the structures firmly establish that type IC topoisomerases form a distinct type of topoisomerases, with no similarities to other types at the sequence, structural, or mechanistic level. They represent a completely different solution to DNA relaxation.
拓扑异构酶 V 是一种独特的拓扑异构酶，它结合了 DNA 修复和拓扑异构酶活性。该酶具有一种不寻常的结构，其小的拓扑异构酶结构域后面跟着 12 个串联（HhH）结构域，其中包括 3 个 AP 核酸内切酶修复结构域。这种酶的不寻常结构与任何其他已知的拓扑异构酶都没有相似之处。在这里，我们展示了拓扑异构酶 V 与 DNA 复合物的结构。这些结构表明，（HhH）结构域围绕 DNA 缠绕，并以这种方式似乎充当了一个持续性因子。该蛋白发生构象变化以暴露拓扑异构酶活性位点。DNA 急剧弯曲进入活性位点，这会使 DNA 熔解，并可能促进松弛。这些结构显示了一种以前未观察到的 DNA 结合模式，并提供了有关这种非典型拓扑异构酶如何松弛 DNA 的信息。与 I 型 B 酶一样，拓扑异构酶 V 使用受控旋转机制松弛 DNA，但这些结构表明拓扑异构酶 V 以不同的方式实现了这一点。总体而言，这些结构明确表明，IIC 型拓扑异构酶形成了一种独特的拓扑异构酶，在序列、结构或机制水平上与其他类型没有相似之处。它们代表了 DNA 松弛的一种完全不同的解决方案。
