Xie Wei, Blain Katherine Y, Kuo Mario Meng-Chiang, Choe Senyon
Structural Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Protein Pept Lett. 2010 Jul;17(7):867-73. doi: 10.2174/092986610791306706.
Two-component systems (TCS) involving the His-Asp phosphotransfer are commonly utilized for signal transduction in prokaryotes in which the two essential components are a sensor histidine kinase (HK) receptor and a response regulator (RR). Despite great efforts in structural and functional characterization of signal perception mechanisms, the exact signaling mechanisms remain elusive for many TCSs. Mimicking the natural TCS signaling pathways, chimeric receptor kinases and response regulators have been constructed through the process of swapping modular domains of related TCSs. To design chimeras with new signaling pathways, domains from different proteins that have little relationship at the primary structural level but carrying desirable functional properties can be conjoined to engineer novel TCSs. These chimeras maintain the ability to respond to environmental stimulants by regulating protein phosphorylation to produce downstream output signals. Depending on the nature of external signals, chimeric TCSs can serve as a novel tool not only to examine the natural signaling mechanisms in TCSs, but also for industrial and clinical applications.
涉及组氨酸 - 天冬氨酸磷酸转移的双组分系统（TCS）通常用于原核生物的信号转导，其中两个关键组分是传感组氨酸激酶（HK）受体和响应调节因子（RR）。尽管在信号感知机制的结构和功能表征方面付出了巨大努力，但许多TCS的确切信号传导机制仍然难以捉摸。通过交换相关TCS的模块化结构域的过程，构建了嵌合受体激酶和响应调节因子，以模拟天然TCS信号通路。为了设计具有新信号通路的嵌合体，可以将来自在一级结构水平上几乎没有关系但具有理想功能特性的不同蛋白质的结构域连接起来，以构建新型TCS。这些嵌合体通过调节蛋白质磷酸化以产生下游输出信号，保持对环境刺激作出反应的能力。根据外部信号的性质，嵌合TCS不仅可以作为研究TCS中天然信号传导机制的新型工具，还可用于工业和临床应用。
