A protonation-coupled feedback mechanism controls the signalling process in bathy phytochromes
A protonation-coupled feedback mechanism controls the signalling process in bathy phytochromes
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DOI：
10.1038/nchem.2225
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发表时间：
2015-05-01
期刊：
影响因子：
21.8
通讯作者：
Hildebrandt, Peter
中科院分区：
文献类型：
--
作者：
Escobar, Francisco Velazquez;Piwowarski, Patrick;Hildebrandt, Peter
光敏染料是由光电传感器和输出模块组成的双模态光开关。传感器的光活化是由四吡咯发色团的双键异构化引发的，并最终导致蛋白质构象的变化。最近确定的光敏色素的结构模型确定的非活性和信号状态之间的差异，但没有揭示光敏元件激活或失活的机制。在这里，我们报告了一个振动光谱的研究表明，形成的光活化状态，从而（去）激活的输出模块是基于质子易位的发色团口袋耦合发色团和蛋白质结构的变化。这些质子转移步骤，涉及四吡咯和附近的组氨酸，也使热反向异构化的发色团通过酮-烯醇互变异构化，以提供初始的暗态。因此，诱导输出模块的激活（去激活）的相同质子重排同时启动该过程的逆转，对应于负反馈机制。
Phytochromes are bimodal photoswitches composed of a photosensor and an output module. Photoactivation of the sensor is initiated by a double bond isomerization of the tetrapyrrole chromophore and eventually leads to protein conformational changes. Recently determined structural models of phytochromes identify differences between the inactive and the signalling state but do not reveal the mechanism of photosensor activation or deactivation. Here, we report a vibrational spectroscopic study on bathy phytochromes that demonstrates that the formation of the photoactivated state and thus (de) activation of the output module is based on proton translocations in the chromophore pocket coupling chromophore and protein structural changes. These proton transfer steps, involving the tetrapyrrole and a nearby histidine, also enable thermal back-isomerization of the chromophore via keto-enol tautomerization to afford the initial dark state. Thus, the same proton re-arrangements inducing the (de) activation of the output module simultaneously initiate the reversal of this process, corresponding to a negative feedback mechanism.