Long-range allosteric signaling in red light-regulated diguanylyl cyclases.
Long-range allosteric signaling in red light-regulated diguanylyl cyclases.
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DOI：
10.1126/sciadv.1602498
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发表时间：
2017-03
期刊：
影响因子：
13.6
通讯作者：
Winkler A
中科院分区：
文献类型：
--
作者：
Gourinchas G;Etzl S;Göbl C;Vide U;Madl T;Winkler A
全长细菌光敏色素的结构和动态特性揭示了分子调控机制的细节。大自然已经进化出一种令人惊讶的模块化结构，由具有多种功能的共价连接蛋白质结构域组成，以形成对细胞生存至关重要的复杂细胞网络。感觉模块与酶效应器的耦合允许细胞信号分子直接变构调节以响应不同的刺激。我们展示了与产生环状二聚鸟苷单磷酸的二鸟苷基环化酶相关的红光感应细菌光敏色素的分子细节。阐明全长光敏色素及其酶效应子的第一个晶体结构，结合光诱导构象动力学变化的表征，揭示了变构光调节如何通过卷曲线圈传感器效应器连接体以及中央螺旋脊柱的结构和组成进行微调。我们预计，考虑传感器-效应器耦合的分子原理、超越特征连接子的长度以及动态驱动变构的欣赏将为新型红光调节光遗传学工具的设计开辟新的方向。
Structural and dynamic properties of a full-length bacteriophytochrome reveal details of the molecular regulation mechanism. Nature has evolved an astonishingly modular architecture of covalently linked protein domains with diverse functionalities to enable complex cellular networks that are critical for cell survival. The coupling of sensory modules with enzymatic effectors allows direct allosteric regulation of cellular signaling molecules in response to diverse stimuli. We present molecular details of red light–sensing bacteriophytochromes linked to cyclic dimeric guanosine monophosphate–producing diguanylyl cyclases. Elucidation of the first crystal structure of a full-length phytochrome with its enzymatic effector, in combination with the characterization of light-induced changes in conformational dynamics, reveals how allosteric light regulation is fine-tuned by the architecture and composition of the coiled-coil sensor-effector linker and also the central helical spine. We anticipate that consideration of molecular principles of sensor-effector coupling, going beyond the length of the characteristic linker, and the appreciation of dynamically driven allostery will open up new directions for the design of novel red light–regulated optogenetic tools.