A Light-Oxygen-Voltage Receptor Integrates Light and Temperature

A Light-Oxygen-Voltage Receptor Integrates Light and Temperature
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DOI:
10.1016/j.jmb.2021.167107
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发表时间:
2021-06-25
影响因子:
5.6
通讯作者:
Moeglich, Andreas
Moeglich, Andreas
中科院分区:
生物学2区
文献类型:
--
作者:
Dietler, Julia;Schubert, Roman;Moeglich, Andreas

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感觉光感受器使生物体能够根据光来调整其生理、行为和发育,通常具有时空敏锐度和可逆性。这些特征是使用光感受器作为基因编码执行器来通过光改变异源生物体的状态和特性的基础。归入光遗传学,相关方法能够调节不同的细胞过程,尤其是基因表达。在这里,我们通过与光氧电压(LOV)模块耦合来控制广泛使用的 Tet 阻遏蛋白,这些模块在蓝光下同二聚或解离。因此,抑制可以升高或减轻,从而蛋白质表达受到光的调节。引人注目的是,来自球形红杆菌的同型二聚体 RsLOV 模块不仅在光下解离,而且本质上对温度发生反应。野生型 RsLOV 在 37 摄氏度下的有限光响应在表现出非常相似的光化学和结构的两个变体中得到增强。一种变体将 40 mM 的弱同二聚化亲和力提高了两倍,因此也赋予受体酪氨酸激酶光敏感性。某些光感受器,例如 RsLOV,显然可以兼作温度传感器,这直接影响到它们在光遗传学和生物技术中的应用。如果正确考虑,可以利用温度敏感性来构建信号响应细胞电路。 (C) 2021 Elsevier Ltd. 保留所有权利。
Sensory photoreceptors enable organisms to adjust their physiology, behavior, and development in response to light, generally with spatiotemporal acuity and reversibility. These traits underlie the use of photoreceptors as genetically encoded actuators to alter by light the state and properties of heterologous organisms. Subsumed as optogenetics, pertinent approaches enable regulating diverse cellular processes, not least gene expression. Here, we controlled the widely used Tet repressor by coupling to light-oxygen-voltage (LOV) modules that either homodimerize or dissociate under blue light. Repression could thus be elevated or relieved, and consequently protein expression was modulated by light. Strikingly, the homodimeric RsLOV module from Rhodobacter sphaeroides not only dissociated under light but intrinsically reacted to temperature. The limited light responses of wild-type RsLOV at 37 degrees C were enhanced in two variants that exhibited closely similar photochemistry and structure. One variant improved the weak homodimerization affinity of 40 mM by two-fold and thus also bestowed light sensitivity on a receptor tyrosine kinase. Certain photoreceptors, exemplified by RsLOV, can evidently moonlight as temperature sensors which immediately bears on their application in optogenetics and biotechnology. Properly accounted for, the temperature sensitivity can be leveraged for the construction of signal-responsive cellular circuits. (C) 2021 Elsevier Ltd. All rights reserved.