Temperate bacteriophages can enter one of two life cycles following infection of a sensitive host: the lysogenic or the lytic life cycle. The choice between the two alternative life cycles is dependent upon a tight regulation of promoters and their cognate regulatory proteins within the phage genome. We investigated the genetic switch of TP901-1, a bacteriophage of Lactococcus lactis, controlled by the CI repressor and the modulator of repression (MOR) antirepressor and their interactions with DNA. We determined the solution structure of MOR, and we solved the crystal structure of MOR in complex with the N-terminal domain of CI, revealing the structural basis of MOR inhibition of CI binding to the DNA operator sites. ¹⁵N NMR Carr–Purcell–Meiboom–Gill (CPMG) relaxation dispersion and rotating frame R_1ρ measurements demonstrate that MOR displays molecular recognition dynamics on two different time scales involving a repacking of aromatic residues at the interface with CI. Mutations in the CI:MOR binding interface impair complex formation in vitro, and when introduced in vivo, the bacteriophage switch is unable to choose the lytic life cycle showing that the CI:MOR complex is essential for proper functioning of the genetic switch. On the basis of sequence alignments, we show that the structural features of the MOR:CI complex are likely conserved among a larger family of bacteriophages from human pathogens implicated in transfer of antibiotic resistance.

在感染敏感宿主后，温带噬菌体可以进入两个生命周期之一：溶原性或裂解性生命周期。在两个替代生命周期之间的选择取决于在噬菌体基因组内对启动子及其同源调节蛋白的严格调节。我们研究了TP901-1（一种乳酸乳球菌的噬菌体）的遗传转换，该噬菌体受CI阻遏物和阻遏物（MOR）抗阻遏物的调节剂控制，以及它们与DNA的相互作用。我们确定了MOR的溶液结构，并解决了与CI的N端结构域复合的MOR的晶体结构，揭示了MOR抑制CI结合到DNA操纵子位点的结构基础。¹⁵ÑNMR卡尔赛尔-Meiboom-吉尔（CPMG）松弛分散和旋转框架ř _1ρ测量表明，在两个不同的时间尺度MOR显示器分子识别动力学在与CI的界面涉及芳族残基的重新包装。CI：MOR结合界面的突变会在体外损害复合物的形成，而在体内引入时，噬菌体开关无法选择裂解生命周期，这表明CI：MOR复合物对于基因开关的正常运转至关重要。在序列比对的基础上，我们表明，MOR：CI复合物的结构特征很可能在来自人类病原体的较大噬菌体家族中保守，涉及细菌耐药性的转移。