Instituto de Biomedicina de Valencia (IBV-CSIC) and CIBER de Enfermedades Raras (CIBERER), 46010 Valencia, Spain.
Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TA, UK.
Mol Cell. 2019 Apr 4;74(1):59-72.e3. doi: 10.1016/j.molcel.2019.01.025. Epub 2019 Feb 7.
Bacillus phages use a communication system, termed "arbitrium," to coordinate lysis-lysogeny decisions. Arbitrium communication is mediated by the production and secretion of a hexapeptide (AimP) during lytic cycle. Once internalized, AimP reduces the expression of the negative regulator of lysogeny, AimX, by binding to the transcription factor, AimR, promoting lysogeny. We have elucidated the crystal structures of AimR from the Bacillus subtilis SPbeta phage in its apo form, bound to its DNA operator and in complex with AimP. AimR presents intrinsic plasticity, sharing structural features with the RRNPP quorum-sensing family. Remarkably, AimR binds to an unusual operator with a long spacer that interacts nonspecifically with the receptor TPR domain, while the HTH domain canonically recognizes two inverted repeats. AimP stabilizes a compact conformation of AimR that approximates the DNA-recognition helices, preventing AimR binding to the aimX promoter region. Our results establish the molecular basis of the arbitrium communication system.
芽孢杆菌噬菌体利用一种称为“仲裁”的通讯系统来协调裂解-溶原决策。仲裁通讯是通过在裂解周期中产生和分泌六肽（AimP）来介导的。一旦被内化，AimP 通过与转录因子 AimR 结合，降低溶原负调控因子 AimX 的表达，从而促进溶原。我们已经阐明了来自枯草芽孢杆菌 SPbeta 噬菌体的 AimR 在其apo 形式、与 DNA 操纵子结合以及与 AimP 复合物中的晶体结构。AimR 具有内在的可塑性，与 RRNPP 群体感应家族共享结构特征。值得注意的是，AimR 与具有长间隔子的不寻常操纵子结合，该间隔子与受体 TPR 结构域非特异性相互作用，而 HTH 结构域则规范地识别两个反向重复。AimP 稳定 AimR 的紧凑构象，近似于 DNA 识别螺旋，从而防止 AimR 与 aimX 启动子区域结合。我们的研究结果确立了仲裁通讯系统的分子基础。
