Departamento de Genética Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México City, México.
Biochem Soc Trans. 2022 Dec 16;50(6):1859-1873. doi: 10.1042/BST20220848.
Two-component systems (TCSs) are modular signaling circuits that regulate diverse aspects of microbial physiology in response to environmental cues. These molecular circuits comprise a sensor histidine kinase (HK) protein that contains a conserved histidine residue, and an effector response regulator (RR) protein with a conserved aspartate residue. HKs play a major role in bacterial signaling, since they perceive specific stimuli, transmit the message across the cytoplasmic membrane, and catalyze their own phosphorylation, and the trans-phosphorylation and dephosphorylation of their cognate response regulator. The molecular mechanisms by which HKs co-ordinate these functions have been extensively analyzed by genetic, biochemical, and structural approaches. Here, we describe the most common modular architectures found in bacterial HKs, and address the operation mode of the individual functional domains. Finally, we discuss the use of these signaling proteins as drug targets or as sensing devices in whole-cell biosensors with medical and biotechnological applications.
双组分系统（TCSs）是模块化的信号转导回路，可响应环境线索调节微生物生理学的各个方面。这些分子回路由传感器组氨酸激酶（HK）蛋白组成，该蛋白包含保守的组氨酸残基，以及效应器响应调节剂（RR）蛋白，该蛋白具有保守的天冬氨酸残基。HK 在细菌信号转导中起着重要作用，因为它们可以感知特定的刺激，将信息穿过细胞质膜传递，并催化自身磷酸化，以及其同源反应调节剂的转磷酸化和去磷酸化。通过遗传、生化和结构方法广泛分析了 HK 协调这些功能的分子机制。在这里，我们描述了在细菌 HK 中发现的最常见的模块化架构，并讨论了各个功能域的操作模式。最后，我们讨论了这些信号蛋白在医学和生物技术应用的全细胞生物传感器中作为药物靶点或传感装置的用途。
