Department of Chemistry - BMC, Biochemistry, Uppsala University, 75123 Uppsala, Sweden.
Nanoscience Center, Department of Biological and Environmental Science, University of Jyväskylä, 40014 Jyväskylä, Finland.
Structure. 2024 Nov 7;32(11):1952-1962.e3. doi: 10.1016/j.str.2024.08.008. Epub 2024 Aug 30.
Phytochromes are photoreceptor proteins in plants, fungi, and bacteria. They can adopt two photochromic states with differential biochemical responses. The structural changes transducing the signal from the chromophore to the biochemical output modules are poorly understood due to challenges in capturing structures of the dynamic, full-length protein. Here, we present cryoelectron microscopy (cryo-EM) structures of the phytochrome from Pseudomonas aeruginosa (PaBphP) in its resting (Pfr) and photoactivated (Pr) state. The kinase-active Pr state has an asymmetric, dimeric structure, whereas the kinase-inactive Pfr state opens up. This behavior is different from other known phytochromes and we explain it with the unusually short connection between the photosensory and output modules. Multiple sequence alignment of this region suggests evolutionary optimization for different modes of signal transduction in sensor proteins. The results establish a new mechanism for light-sensing by phytochrome histidine kinases and provide input for the design of optogenetic phytochrome variants.
植物光敏色素是植物、真菌和细菌中的光受体蛋白。它们可以采用两种具有不同生化反应的光致变色状态。由于难以捕捉动态全长蛋白质的结构，因此信号从发色团传递到生化输出模块的结构变化仍知之甚少。在这里，我们展示了铜绿假单胞菌（Pseudomonas aeruginosa）光敏色素（PaBphP）在其静止（Pfr）和光激活（Pr）状态的冷冻电镜（cryo-EM）结构。激酶活性的 Pr 状态具有不对称的二聚体结构，而激酶非活性的 Pfr 状态则会打开。这种行为与其他已知的光敏色素不同，我们用感光和输出模块之间异常短的连接来解释它。该区域的多序列比对表明，传感器蛋白中的信号转导模式存在进化优化。该结果为光敏色素组氨酸激酶的光感应建立了一种新的机制，并为光遗传学光敏色素变体的设计提供了依据。
