Signaling molecule receptors play a central role in quorum sensing and in the coordination onset of specialized metabolite biosynthesis in Streptomyces due to their dual function in signal detection and gene expression control through DNA-binding in the promoter region of their target genes. In Streptomyces ambofaciens the alp biosynthetic gene cluster includes the signaling molecule receptor AlpZ that negatively regulates through a complex regulatory cascade the expression of key genes involved in the kinamycin antibiotic production until its cognate ligand, a yet unidentified signaling molecule, prompts its release from target promoters. Here we use an original molecular dynamics method to evaluate the DNA-binding properties of AlpZ to its target DNA sequence and the impact the signaling molecule has on the interaction. It is the first time this approach is used to characterize a regulator from the γ-butyrolactone receptor family. The observed K_D in the nanomolar range indicates that AlpZ-DNA constitute a particularly stable complex. The signaling molecule ably disturbs this binding while kinamycin has no effect on the activity of AlpZ. Regulator size was determined and found to be considerably large regarding protein sequence, indicating that AlpZ regulates gene expression by binding the DNA as a homodimer, and structural modeling comparison with closely related γ-butyrolactone receptors supports this conclusion.

信号分子受体在群体感应和专门代谢物生物合成的协调发生中起核心作用。 链霉菌由于它们在信号检测和基因表达控制中具有双重功能，原因是它们通过在其靶基因的启动子区域中进行DNA结合来进行控制。在竹链霉菌 的 阿尔卑斯山生物合成基因簇包括信号分子受体AlpZ，该信号分子通过复杂的调控级联反应负调控参与金那霉素抗生素生产的关键基因的表达，直到其同源配体（尚未确定的信号分子）促使其从靶启动子释放。在这里，我们使用原始的分子动力学方法来评估AlpZ与其目标DNA序列的DNA结合特性以及信号分子对相互作用的影响。这是该方法首次用于表征γ-丁内酯受体家族的调节剂。观察到的K _D在纳摩尔范围内的“α”表示AlpZ-DNA构成特别稳定的复合物。信号分子可以很好地干扰这种结合，而卡那霉素对AlpZ的活性没有影响。确定了调节子的大小，并发现其在蛋白质序列方面相当大，表明AlpZ通过结合DNA作为同源二聚体来调节基因表达，并且与密切相关的γ-丁内酯受体的结构模型比较支持了这一结论。