Trajtenberg Felipe, Buschiazzo Alejandro
Laboratory of Molecular and Structural Microbiology, Institut Pasteur de Montevideo, Montevideo, Uruguay.
Département de Microbiologie, Institut Pasteur, Paris, France.
Methods Mol Biol. 2020;2077:1-18. doi: 10.1007/978-1-4939-9884-5_1.
The ability to perceive the environment, an essential attribute in living organisms, is linked to the evolution of signaling proteins that recognize specific signals and execute predetermined responses. Such proteins constitute concerted systems that can be as simple as a unique protein, able to recognize a ligand and exert a phenotypic change, or extremely complex pathways engaging dozens of different proteins which act in coordination with feedback loops and signal modulation. To understand how cells sense their surroundings and mount specific adaptive responses, we need to decipher the molecular workings of signal recognition, internalization, transfer, and conversion into chemical changes inside the cell. Protein allostery and dynamics play a central role. Here, we review recent progress on the study of two-component systems, important signaling machineries of prokaryotes and lower eukaryotes. Such systems implicate a sensory histidine kinase and a separate response regulator protein. Both components exploit protein flexibility to effect specific conformational rearrangements, modulating protein-protein interactions, and ultimately transmitting information accurately. Recent work has revealed how histidine kinases switch between discrete functional states according to the presence or absence of the signal, shifting key amino acid positions that define their catalytic activity. In concert with the cognate response regulator's allosteric changes, the phosphoryl-transfer flow during the signaling process is exquisitely fine-tuned for proper specificity, efficiency and directionality.
感知环境的能力是生物的一项基本属性，它与识别特定信号并执行预定反应的信号蛋白的进化相关联。这类蛋白构成了协同系统，其简单程度可低至一种能够识别配体并引发表型变化的单一蛋白，也可以是极其复杂的通路，涉及数十种不同蛋白，这些蛋白通过反馈回路和信号调节协同作用。为了理解细胞如何感知周围环境并做出特定的适应性反应，我们需要破解信号识别、内化、传递以及转化为细胞内化学变化的分子机制。蛋白质别构和动力学起着核心作用。在此，我们综述了关于双组分系统研究的最新进展，双组分系统是原核生物和低等真核生物重要的信号传导机制。这类系统涉及一个传感组氨酸激酶和一个单独的反应调节蛋白。这两个组分利用蛋白质的灵活性实现特定的构象重排，调节蛋白质 - 蛋白质相互作用，并最终准确地传递信息。最近的研究揭示了组氨酸激酶如何根据信号的有无在不同的功能状态之间切换，移动决定其催化活性的关键氨基酸位置。与同源反应调节蛋白的别构变化协同，信号传导过程中的磷酸转移流被精确微调，以实现适当的特异性、效率和方向性。
