The recognition domain of the methyl-specific endonuclease McrBC flips out 5-methylcytosine.
The recognition domain of the methyl-specific endonuclease McrBC flips out 5-methylcytosine.
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DOI：
10.1093/nar/gks332
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发表时间：
2012-08
影响因子：
14.9
通讯作者：
Siksnys V
中科院分区：
文献类型：
--
作者：
Sukackaite R;Grazulis S;Tamulaitis G;Siksnys V
DNA胞嘧啶甲基化是一种广泛存在的表观遗传标记。DNA甲基化的生物学效应由在不同序列背景下优先结合5-甲基胞嘧啶（5 mC）的蛋白质介导。到目前为止，已经建立了两种不同的结构机制在真核生物中的5 mC识别;然而，它仍然是未知的5 mC修饰的歧视是如何实现在原核生物。在这里，我们报告的N-末端DNA结合结构域（McrB-N）的甲基特异性核酸内切酶McrBC从大肠杆菌的晶体结构。McrB-N蛋白显示出适合5 mC识别的新型DNA结合折叠。在与甲基化DNA复合的McrB-N结构中，5 mC碱基从DNA双链体中翻转出来并定位在结合口袋中。碱基翻转巧妙地解释了为什么McrBC系统仅限制糖基化中受损的T4-甚至T4-[Luria，S.E.人类，M。（1952）一种非遗传性的、宿主诱导的细菌病毒变异。J. Bacteriol.，64，557-569]：翻转的5-羟甲基胞嘧啶被容纳在结合口袋中，但没有糖基化碱基的空间。McrB-N采用的5 mC识别机制与真核生物SRA结构域的识别机制非常相似，尽管它们的蛋白质折叠存在差异。
DNA cytosine methylation is a widespread epigenetic mark. Biological effects of DNA methylation are mediated by the proteins that preferentially bind to 5-methylcytosine (5mC) in different sequence contexts. Until now two different structural mechanisms have been established for 5mC recognition in eukaryotes; however, it is still unknown how discrimination of the 5mC modification is achieved in prokaryotes. Here we report the crystal structure of the N-terminal DNA-binding domain (McrB-N) of the methyl-specific endonuclease McrBC from Escherichia coli. The McrB-N protein shows a novel DNA-binding fold adapted for 5mC-recognition. In the McrB-N structure in complex with methylated DNA, the 5mC base is flipped out from the DNA duplex and positioned within a binding pocket. Base flipping elegantly explains why McrBC system restricts only T4-even phages impaired in glycosylation [Luria, S.E. and Human, M.L. (1952) A nonhereditary, host-induced variation of bacterial viruses. J. Bacteriol., 64, 557–569]: flipped out 5-hydroxymethylcytosine is accommodated in the binding pocket but there is no room for the glycosylated base. The mechanism for 5mC recognition employed by McrB-N is highly reminiscent of that for eukaryotic SRA domains, despite the differences in their protein folds.
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DOI：
10.1107/s0907444905036693
发表时间：
2006-01-01
影响因子：
2.2
作者：
Evans, P
通讯作者：
Evans, P
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
14.9
作者：
Dash, C;Rausch, JW;Le Grice, SFJ
通讯作者：
Le Grice, SFJ
影响因子：
13.8
作者：
Combet, C;Blanchet, C;Deléage, G
通讯作者：
Deléage, G
影响因子：
3.7
作者：
Gast, FU;Brinkmann, T;Pingoud, A
通讯作者：
Pingoud, A