Nanoscience Center, Department of Biological and Environmental Science, University of Jyväskylä, 40014, Jyväskylä, Finland.
Institute of Biochemistry, Graz University of Technology, Petersgasse 12/II, 8010, Graz, Austria.
Photochem Photobiol Sci. 2022 Nov;21(11):1881-1894. doi: 10.1007/s43630-022-00265-5. Epub 2022 Aug 19.
Signal transduction typically starts with either ligand binding or cofactor activation, eventually affecting biological activities in the cell. In red light-sensing phytochromes, isomerization of the bilin chromophore results in regulation of the activity of diverse output modules. During this process, several structural elements and chemical events influence signal propagation. In our study, we have studied the full-length bacteriophytochrome from Deinococcus radiodurans as well as a previously generated optogenetic tool where the native histidine kinase output module has been replaced with an adenylate cyclase. We show that the composition of the output module influences the stability of the hairpin extension. The hairpin, often referred as the PHY tongue, is one of the central structural elements for signal transduction. It extends from a distinct domain establishing close contacts with the chromophore binding site. If the coupling between these interactions is disrupted, the dynamic range of the enzymatic regulation is reduced. Our study highlights the complex conformational properties of the hairpin extension as a bidirectional link between the chromophore-binding site and the output module, as well as functional properties of diverse output modules.
信号转导通常始于配体结合或辅助因子激活，最终影响细胞中的生物活性。在红光感应的光敏色素中，双氢卟啉发色团的异构化导致不同输出模块的活性调节。在这个过程中，几个结构元素和化学事件影响信号传递。在我们的研究中，我们研究了来自耐辐射球菌的全长细菌光敏色素，以及之前生成的光遗传学工具，其中天然组氨酸激酶输出模块已被腺苷酸环化酶取代。我们表明，输出模块的组成影响发夹延伸的稳定性。发夹，通常称为 PHY 舌，是信号转导的中心结构元件之一。它从一个独特的结构域延伸出来，与发色团结合位点建立紧密接触。如果这些相互作用的耦合被破坏，酶调节的动态范围将会减小。我们的研究强调了发夹延伸作为发色团结合位点和输出模块之间的双向连接的复杂构象特性，以及不同输出模块的功能特性。
