Structural basis for gene regulation by a B12-dependent photoreceptor.
Structural basis for gene regulation by a B12-dependent photoreceptor.
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DOI：
10.1038/nature14950
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发表时间：
2015-10-22
期刊：
影响因子：
64.8
通讯作者：
Drennan CL
中科院分区：
文献类型：
--
作者：
Jost M;Fernández-Zapata J;Polanco MC;Ortiz-Guerrero JM;Chen PY;Kang G;Padmanabhan S;Elías-Arnanz M;Drennan CL
光感受器蛋白质使生物体能够感知和响应光。新发现的CarH型光感受器使用维生素B12衍生物腺苷钴胺素作为光敏发色团来介导光依赖性基因调控。在这里，我们目前的晶体结构的Thermus thermophilus CarH在所有三个相关的状态：在黑暗中，无论是自由和绑定到运营商DNA，和曝光后。这些结构提供了腺苷钴胺素如何在黑暗中介导CarH四聚体形成的可视化，该四聚体如何与启动子-35元件结合以抑制转录，以及光照如何导致大规模构象变化以激活转录。除了腺苷钴胺素从酶辅因子到光传感器的显着功能再利用之外，我们发现自然界还在组装CarH中重新利用了两个独立的蛋白质模块。这些结果扩展了维生素B12的生物学作用，并为光依赖性基因调控的新模式提供了基本见解。
Photoreceptor proteins enable organisms to sense and respond to light. The newly discovered CarH-type photoreceptors use a vitamin B12 derivative, adenosylcobalamin, as the light-sensing chromophore to mediate light-dependent gene regulation. Here, we present crystal structures of Thermus thermophilus CarH in all three relevant states: in the dark, both free and bound to operator DNA, and after light exposure. These structures provide a visualization of how adenosylcobalamin mediates CarH tetramer formation in the dark, how this tetramer binds to the promoter −35 element to repress transcription, and how light exposure leads to a large-scale conformational change that activates transcription. In addition to the remarkable functional repurposing of adenosylcobalamin from an enzyme cofactor to a light sensor, we find that nature also repurposed two independent protein modules in assembling CarH. These results expand the biological role of vitamin B12 and provide fundamental insight into a new mode of light-dependent gene regulation.