Department of Chemistry and Biochemistry, Florida International University, Miami, FL 33199, USA.
Structural Biology Center, X-ray Science Division, Advanced Photon Source, Argonne National Laboratory, 9700 S. Cass Avenue, Lemont, IL 60439, USA.
Int J Mol Sci. 2022 Aug 5;23(15):8709. doi: 10.3390/ijms23158709.
Type IA topoisomerases have highly conserved catalytic N-terminal domains for the cleaving and rejoining of a single DNA/RNA strand that have been extensively characterized. In contrast, the C-terminal region has been less covered. Two major types of small tandem C-terminal domains, Topo_C_ZnRpt (containing C4 zinc finger) and Topo_C_Rpt (without cysteines) were initially identified in and topoisomerase I, respectively. Their structures and interaction with DNA oligonucleotides have been revealed in structural studies. Here, we first present the diverse distribution and combinations of these two structural elements in various bacterial topoisomerase I (TopA). Previously, zinc fingers have not been seen in type IA topoisomerases from well-studied fungal species within the phylum Ascomycota. In our extended studies of C-terminal DNA-binding domains, the presence of zf-GRF and zf-CCHC types of zinc fingers in topoisomerase III (Top3) from fungi species in many phyla other than Ascomycota has drawn our attention. We secondly analyze the distribution and combination of these fungal zf-GRF- and zf-CCHC-containing domains. Their potential structures and DNA-binding mechanism are evaluated. The highly diverse arrangements and combinations of these DNA/RNA-binding domains in microbial type IA topoisomerase C-terminal regions have important implications for their interactions with nucleic acids and protein partners as part of their physiological functions.
I 型拓扑异构酶具有高度保守的催化 N 端结构域，可用于单链 DNA/RNA 的切割和连接，该结构域已得到广泛研究。相比之下，C 端区域的研究较少。最初在 和 拓扑异构酶 I 中分别鉴定出两种主要类型的小串联 C 端结构域，Topo_C_ZnRpt（含有 C4 锌指）和 Topo_C_Rpt（不含半胱氨酸）。在结构研究中揭示了它们的结构及其与 DNA 寡核苷酸的相互作用。在这里，我们首先介绍了这两种结构元件在各种细菌拓扑异构酶 I（TopA）中的不同分布和组合。以前，锌指在门子囊菌中的研究较多的真菌物种的 I 型拓扑异构酶中尚未见报道。在我们对 C 端 DNA 结合结构域的扩展研究中，我们注意到来自除子囊菌以外的许多门真菌物种的拓扑异构酶 III（Top3）中存在 zf-GRF 和 zf-CCHC 型锌指。我们其次分析了这些真菌 zf-GRF 和 zf-CCHC 含域的分布和组合。评估了它们的潜在结构和 DNA 结合机制。这些微生物 I 型拓扑异构酶 C 端区域中 DNA/RNA 结合结构域的高度多样化排列和组合对它们与核酸和蛋白质伙伴的相互作用具有重要意义，这是它们生理功能的一部分。
