Structural elucidation of a novel mechanism for bacteriophage-based inhibition of the RNA degradosome

In all domains of life, the catalysed degradation of RNA facilitates rapid adaption to changing environmental conditions. We identified a virus-encoded protein that directly binds and inhibits the RNA degradation machinery of its bacterial host, allowing efficient accumulation of viral RNA in the infected cell. Encoded by the giant phage фKZ, KZ37/Dip associates with two RNA binding sites of the RNase E component of the Pseudomonas aeruginosa RNA degradosome. Thereby, KZ37/Dip competes with the binding of RNA substrates, resulting in effective inhibition of RNA degradation. The crystal structure of KZ37/Dip (2.2 Å) reveals an unprecedented fold for which there are no identified structural homologues. The protein forms a homo-dimer that resembles a partially opened scroll and binds RNase E through exposed acidic patches on its convex outer surface. Through the activity of KZ37/Dip, фKZ has evolved a unique mechanism to down regulate a key process of its host.

在所有生命域中，酶促RNA降解过程可帮助生物体快速适应不断变化的环境条件。本研究鉴定出一种病毒编码蛋白，该蛋白可直接结合并抑制其细菌宿主的RNA降解系统，使病毒RNA能够在感染细胞内高效积累。该蛋白由巨型噬菌体фKZ编码，KZ37/Dip可结合铜绿假单胞菌RNA降解体（RNA degradosome）中核糖核酸酶E（RNase E）的两个RNA结合位点。借此，KZ37/Dip可竞争性结合RNA底物，从而有效抑制RNA降解过程。KZ37/Dip的晶体结构（分辨率2.2埃（Å））展现出一种前所未有的折叠构象，目前尚未发现与之匹配的结构同源物。该蛋白以同源二聚体形式存在，其结构类似半开的卷轴，并通过凸向外表面上暴露的酸性区域与RNase E结合。借助KZ37/Dip的活性，巨型噬菌体фKZ进化出了一种独特的机制，可下调宿主的关键生理过程。