Three-dimensional structure of the diphtheria toxin repressor in complex with divalent cation co-repressors.
Three-dimensional structure of the diphtheria toxin repressor in complex with divalent cation co-repressors.
复制标题
白喉毒素阻遏物与二价阳离子共阻遏物复合物的三维结构。
DOI：
10.1016/s0969-2126(01)00137-x
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Hol,WG
中科院分区：
文献类型：
--
作者：
Qiu,X;Verlinde,CL;Zhang,S;Schmitt,MP;Holmes,RK;Hol,WG
背景：白喉棒状杆菌在低浓度铁离子环境中能启动白喉毒素等毒力因子的合成。白喉毒素阻遏物（DtxR）在该铁依赖性全局调节系统中起关键作用，并且是革兰氏阳性细菌中铁依赖性阻遏蛋白的新家族的原型。这项研究的目的是增加了解的一般监管原则的阳离子结合DtxR.ResultsThe晶体结构的二聚体DtxR全阻遏物在复杂的不同过渡金属显示，每个亚基包括一个氨基末端的DNA结合域，界面域（其中包含两个金属结合位点）和第三个，非常灵活的羧基末端域。每个DNA结合结构域都包含螺旋-转角-螺旋基序，并且具有与分解代谢物基因激活蛋白（CAP）非常相似的拓扑结构。分子模拟表明，结合的DNA采用弯曲的构象与螺旋α3的DtxR与大沟相互作用。两个金属结合位点相距约10 μ m。结合位点2位于DNA结合和界面结构域之间的潜在铰链区。残基98-108似乎是至关重要的阻遏物的功能，这些提供了四个配体的两个金属结合位点和三个残基在另一侧的螺旋，这是在二聚体interfaces.ConclusionThe的DtxR holo-repressor的晶体结构表明，二价阳离子共阻遏物控制运动的DNA结合域。以这种方式，金属辅阻遏物控制两个亚基中操纵子识别元件之间的距离，从而控制DNA识别。
Background:WhenCorynebacterium diphtheriaeencounters an environment with a low concentration of iron ions, it initiates the synthesis of several virulence factors, including diphtheria toxin. The diphtheria toxin repressor (DtxR) plays a key role in this iron–dependent, global regulatory system and is the prototype for a new family of iron –dependent repressor proteins in Gram-positive bacteria. This study aimed to increase understanding of the general regulatory principles of cation binding to DtxR.ResultsThe crystal structure of dimeric DtxR holo-repressor in complex with different transition metals shows that each subunit comprises an amino-terminal DNA–binding domain, an interface domain (which contains two metal-binding sites) and a third, very flexible carboxy-terminal domain. Each DNA–binding domain contains a helix–turn–helix motif and has a topology which is very similar to catabolite gene activator protein (CAP). Molecular modeling suggests that bound DNA adopts a bent conformation with helicesα3 of DtxR interacting with the major grooves. The two metal-binding sites lie ∼10 Å apart. Binding site 2 is positioned at a potential hinge region between the DNA–binding and interface domains. Residues 98–108 appear to be crucial for the functioning of the repressor; these provide four of the ligands of the two metal-binding sites and three residues at the other side of the helix which are at the heart of the dimer interface.ConclusionThe crystal structure of the DtxR holo-repressor suggests that the divalent cation co–repressor controls motions of the DNA-binding domain. In this way the metal co–repressor governs the distance between operator recognition elements in the two subunits and, consequently, DNA recognition.