Wang Zhihao, Wang Hongliang, Mulvenna Nancy, Sanz-Hernandez Maximo, Zhang Peipei, Li Yanqing, Ma Jia, Wang Yawen, Matthews Steve, Wigneshweraraj Sivaramesh, Liu Bing
BioBank, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, United Kingdom.
Front Microbiol. 2021 Jun 2;12:692512. doi: 10.3389/fmicb.2021.692512. eCollection 2021.
DNA mimicry by proteins is a strategy that employed by some proteins to occupy the binding sites of the DNA-binding proteins and deny further access to these sites by DNA. Such proteins have been found in bacteriophage, eukaryotic virus, prokaryotic, and eukaryotic cells to imitate non-coding functions of DNA. Here, we report another phage protein Gp44 from bacteriophage SPO1 of , employing mimicry as part of unusual strategy to inhibit host RNA polymerase. Consisting of three simple domains, Gp44 contains a DNA binding motif, a flexible DNA mimic domain and a random-coiled domain. Gp44 is able to anchor to host genome and interact bacterial RNA polymerase the β and β' subunit, resulting in bacterial growth inhibition. Our findings represent a non-specific strategy that SPO1 phage uses to target different bacterial transcription machinery regardless of the structural variations of RNA polymerases. This feature may have potential applications like generation of genetic engineered phages with Gp44 gene incorporated used in phage therapy to target a range of bacterial hosts.
蛋白质的DNA模拟是一些蛋白质采用的一种策略，用于占据DNA结合蛋白的结合位点，并阻止DNA进一步进入这些位点。已在噬菌体、真核病毒、原核细胞和真核细胞中发现此类蛋白质可模仿DNA的非编码功能。在此，我们报道了来自噬菌体SPO1的另一种噬菌体蛋白Gp44，它采用模拟作为一种不同寻常的策略来抑制宿主RNA聚合酶。Gp44由三个简单结构域组成，包含一个DNA结合基序、一个灵活的DNA模拟结构域和一个无规卷曲结构域。Gp44能够锚定到宿主基因组并与细菌RNA聚合酶的β和β'亚基相互作用，从而导致细菌生长抑制。我们的发现代表了SPO1噬菌体用于靶向不同细菌转录机制的一种非特异性策略，而不考虑RNA聚合酶的结构变化。这一特性可能具有潜在应用，比如生成整合了Gp44基因的基因工程噬菌体，用于噬菌体疗法以靶向一系列细菌宿主。
