A redox-controlled molecular switch revealed by the crystal structure of a bacterial heme PAS sensor
A redox-controlled molecular switch revealed by the crystal structure of a bacterial heme PAS sensor
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DOI：
10.1074/jbc.m314199200
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发表时间：
2004-05-07
影响因子：
4.8
通讯作者：
Shimizu, T
中科院分区：
文献类型：
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作者：
Kurokawa, H;Lee, DS;Shimizu, T
PAS结构域，已被确定在1100多个蛋白质从所有三个王国的生活，转换各种输入刺激信号传播到下游组件通过修改蛋白质-蛋白质相互作用。一种这样的蛋白质是大肠杆菌氧化还原传感器，Ec DOS，一种以氧化还原依赖性方式降解环腺苷一磷酸的磷酸二酯酶。在这里，我们报告的晶体结构的血红素PAS域的Ec DOS在两个非活性Fe 3+和活性Fe 2+的形式，分别在1.32和1.9埃的分辨率。该蛋白折叠成特征性PAS结构域结构并形成同源二聚体。在Fe 3+形式中，血红素铁连接到His-77侧链和水分子。血红素铁还原伴随着血红素-配体从水分子转换到来自FG环的Met-95的侧链。同时，柔性FG环被显著地硬化，沿着伴随着氢键模式和亚基相对于彼此的旋转的变化。目前的数据使我们提出了一种新的氧化还原调节的分子开关，其中本地血红素配体开关可能会引发一个全球性的“剪刀型”亚基运动，促进催化控制。
PAS domains, which have been identified in over 1100 proteins from all three kingdoms of life, convert various input stimuli into signals that propagate to downstream components by modifying protein-protein interactions. One such protein is the Escherichia coli redox sensor, Ec DOS, a phosphodiesterase that degrades cyclic adenosine monophosphate in a redox-dependent manner. Here we report the crystal structures of the heme PAS domain of Ec DOS in both inactive Fe3+ and active Fe2+ forms at 1.32 and 1.9 Angstrom resolution, respectively. The protein folds into a characteristic PAS domain structure and forms a homodimer. In the Fe3+ form, the heme iron is ligated to a His-77 side chain and a water molecule. Heme iron reduction is accompanied by heme-ligand switching from the water molecule to a side chain of Met-95 from the FG loop. Concomitantly, the flexible FG loop is significantly rigidified, along with a change in the hydrogen bonding pattern and rotation of subunits relative to each other. The present data led us to propose a novel redox-regulated molecular switch in which local heme-ligand switching may trigger a global "scissor-type" subunit movement that facilitates catalytic control.