Western Carolina University, Department of Chemistry and Physics, 111 Memorial Drive, Cullowhee, NC, 28723, USA.
Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, 48109, USA.
Nat Commun. 2022 Jul 14;13(1):4105. doi: 10.1038/s41467-022-31678-6.
Regulation of bacteriophage gene expression involves repressor proteins that bind and downregulate early lytic promoters. A large group of mycobacteriophages code for repressors that are unusual in also terminating transcription elongation at numerous binding sites (stoperators) distributed across the phage genome. Here we provide the X-ray crystal structure of a mycobacteriophage immunity repressor bound to DNA, which reveals the binding of a monomer to an asymmetric DNA sequence using two independent DNA binding domains. The structure is supported by small-angle X-ray scattering, DNA binding, molecular dynamics, and in vivo immunity assays. We propose a model for how dual DNA binding domains facilitate regulation of both transcription initiation and elongation, while enabling evolution of other superinfection immune specificities.
噬菌体基因表达的调控涉及到结合并下调早期裂解启动子的抑制蛋白。一大组分枝杆菌噬菌体编码的抑制蛋白也不寻常，它们在噬菌体基因组上的许多结合位点（操纵子）上终止转录延伸。在这里，我们提供了一个分枝杆菌噬菌体免疫抑制剂与 DNA 结合的 X 射线晶体结构，该结构揭示了一个单体使用两个独立的 DNA 结合域与不对称 DNA 序列的结合。该结构得到了小角 X 射线散射、DNA 结合、分子动力学和体内免疫测定的支持。我们提出了一个模型，说明双 DNA 结合域如何促进转录起始和延伸的调节，同时使其他超感染免疫特异性得以进化。
