Structural insights into DNA recognition by AimR of the arbitrium communication system in the SPbeta phage
Structural insights into DNA recognition by AimR of the arbitrium communication system in the SPbeta phage
复制标题
SPbeta 噬菌体中仲裁通讯系统 AimR 识别 DNA 的结构见解
DOI：
10.1038/s41421-019-0101-2
复制
发表时间：
2019-05-28
期刊：
影响因子：
33.5
通讯作者：
Zou, Tingting
中科院分区：
文献类型：
--
作者：
Guan, Zeyuan;Pei, Kai;Zou, Tingting
一个新发现的仲裁通信系统调节芽孢杆菌噬菌体的裂解-溶原性决定。该系统包含作为信号的六肽、细胞受体AimR和溶原性负调节因子AimX。AimR特异性靶向下游DNA以激活aimX基因表达。arbitrium肽与AimR结合，抑制其DNA结合以促进噬菌体溶原性。最近，我们和其他小组已经阐明了AimR如何感知任意肽。然而，AimR识别DNA的分子机制以及肽对DNA结合活性的调节在很大程度上仍然未知。在这里，我们报告了AimR-DNA复合物在2.1埃分辨率下的晶体结构。N-末端H T H基序识别回文DNA序列，由带正电荷的残基和DNA磷酸基团之间的相互作用支持。DNA结合的AimR组装成比肽结合形式更封闭的二聚体。单分子FRET和交联分析表明，AimR蛋白样品在溶液中的开放和闭合构象。Arbitrium肽结合诱导AimR的闭合到开放构象变化，消除DNA靶向。我们的结构和功能分析提供了新的见解的DNA识别机制的AimR和其调控的arbitrium肽的背景下，噬菌体裂解溶原性的决定。
A newly identified arbitrium communication system regulates the lysis-to-lysogeny decision in a Bacillus bacteriophage. This system contains an arbitrium hexapeptide as a signal, the cellular receptor AimR, and the lysogenic negative regulator AimX. AimR specifically targets the downstream DNA to activate aimX gene expression. The arbitrium peptide binds to AimR, inhibiting its DNA-binding to promote phage lysogeny. Recently, we and other groups have elucidated how arbitrium peptide sensed by AimR. However, the molecular mechanisms of DNA recognition by AimR and the regulation of its DNA-binding activity by the peptide remain largely unknown. Here, we report the crystal structure of the AimR-DNA complex at 2.1 angstrom resolution. The N-terminal H T H motif recognizes the palindromic DNA sequence, buttressed by interactions between positively charged residues and the DNA phosphate groups. The DNA-bound AimR assembles a more closed dimer than the peptide-bound form. Single-molecule FRET and crosslinking assays revealed that the AimR protein samples both open and closed conformations in solution. Arbitrium peptide binding induces a closed-to-open conformational change of AimR, eliminating DNA targeting. Our structural and functional analysis provides new insights into the DNA recognition mechanism of AimR and its regulation by the arbitrium peptide in the context of phage lysis-lysogeny decisions.