Gjorgjevikj Daniela, Kumar Naveen, Wang Bing, Hilal Tarek, Said Nelly, Loll Bernhard, Artsimovitch Irina, Sen Ranjan, Wahl Markus C
Laboratory of Structural Biochemistry, Institute of Chemistry and Biochemistry, Freie Universität Berlin, Berlin, Germany.
Department of Medicine, Molecular Immunity Unit, MRC Laboratory of Molecular Biology, University of Cambridge, Cambridge, UK.
Nat Commun. 2025 Jan 9;16(1):550. doi: 10.1038/s41467-025-55897-9.
Many bacteriophages modulate host transcription to favor expression of their own genomes. Phage satellite P4 polarity suppression protein, Psu, a building block of the viral capsid, inhibits hexameric transcription termination factor, ρ, by presently unknown mechanisms. Our cryogenic electron microscopy structures of ρ-Psu complexes show that Psu dimers clamp two inactive, open ρ rings and promote their expansion to higher-oligomeric states. ATPase, nucleotide binding and nucleic acid binding studies revealed that Psu hinders ρ ring closure and traps nucleotides in their binding pockets on ρ. Structure-guided mutagenesis in combination with growth, pull-down, and termination assays further delineated the functional ρ-Psu interfaces in vivo. Bioinformatic analyses revealed that Psu is associated with a wide variety of phage defense systems across Enterobacteriaceae, suggesting that Psu may regulate expression of anti-phage genes. Our findings show that modulation of the ρ oligomeric state via diverse strategies is a pervasive gene regulatory principle in bacteria.
许多噬菌体调节宿主转录以促进其自身基因组的表达。噬菌体卫星P4极性抑制蛋白Psu是病毒衣壳的组成部分，它通过目前未知的机制抑制六聚体转录终止因子ρ。我们的ρ-Psu复合物的低温电子显微镜结构表明，Psu二聚体夹住两个无活性的开放ρ环，并促进它们扩展到更高的寡聚状态。ATP酶、核苷酸结合和核酸结合研究表明，Psu阻碍ρ环的闭合，并将核苷酸捕获在ρ上的结合口袋中。结合生长、下拉和终止试验的结构导向诱变进一步在体内描绘了功能性的ρ-Psu界面。生物信息学分析表明，Psu与肠杆菌科中广泛的噬菌体防御系统相关，这表明Psu可能调节抗噬菌体基因的表达。我们的研究结果表明，通过多种策略调节ρ的寡聚状态是细菌中普遍存在的基因调控原理。
