Mesh : Histidine Kinase / metabolism genetics Signal Transduction Phosphoric Monoester Hydrolases / metabolism genetics Phosphorylation Bacterial Proteins / metabolism genetics Escherichia coli / metabolism genetics

来  源:   DOI:10.1038/s41467-024-49251-8   PDF(Pubmed)

Abstract:
Bacteria must constantly probe their environment for rapid adaptation, a crucial need most frequently served by two-component systems (TCS). As one component, sensor histidine kinases (SHK) control the phosphorylation of the second component, the response regulator (RR). Downstream responses hinge on RR phosphorylation and can be highly stringent, acute, and sensitive because SHKs commonly exert both kinase and phosphatase activity. With a bacteriophytochrome TCS as a paradigm, we here interrogate how this catalytic duality underlies signal responses. Derivative systems exhibit tenfold higher red-light sensitivity, owing to an altered kinase-phosphatase balance. Modifications of the linker intervening the SHK sensor and catalytic entities likewise tilt this balance and provide TCSs with inverted output that increases under red light. These TCSs expand synthetic biology and showcase how deliberate perturbations of the kinase-phosphatase duality unlock altered signal-response regimes. Arguably, these aspects equally pertain to the engineering and the natural evolution of TCSs.
摘要:
细菌必须不断探测它们的环境以快速适应,双组分系统(TCS)最常见的关键需求。作为一个组成部分,传感器组氨酸激酶(SHK)控制第二组分的磷酸化,响应调节器(RR)。下游反应取决于RR磷酸化,可以是高度严格的,急性,并且敏感,因为SHK通常同时发挥激酶和磷酸酶活性。以细菌色素TCS为范例,我们在这里询问这种催化对偶性如何成为信号响应的基础。导数系统表现出高十倍的红光灵敏度,由于激酶-磷酸酶平衡的改变。插入SHK传感器和催化实体的连接体的修饰同样使这种平衡倾斜,并提供具有在红光下增加的反向输出的TCS。这些TCS扩展了合成生物学,并展示了激酶-磷酸酶二元性的故意扰动如何解锁改变的信号反应机制。可以说,这些方面同样与TCS的工程和自然演变有关。
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