MeCP2 binding to DNA depends upon hydration at methyl-CpG
MeCP2 binding to DNA depends upon hydration at methyl-CpG
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DOI：
10.1016/j.molcel.2007.12.028
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发表时间：
2008-02-29
期刊：
影响因子：
16
通讯作者：
Walkinshaw, Malcolm D.
中科院分区：
文献类型：
--
作者：
Ho, Kok Lian;McNae, Lain W.;Walkinshaw, Malcolm D.
MeCP 2是一种重要的转录抑制因子，通过与甲基化DNA结合介导基因沉默。结合特异性被认为取决于胞嘧啶甲基和甲基-CpG结合结构域（MBD）内的疏水补丁之间的疏水相互作用。然而，甲基化DNA-MBD共晶体的X射线分析显示，甲基与主要亲水性表面接触，该表面包括紧密结合的水分子。这表明MeCP 2识别甲基化DNA的大沟的水合作用，而不是胞嘧啶甲基化本身。MeCP 2-DNA复合物还确定了T158的独特结构作用，T158是Rett综合征中最常见的突变残基。
MeCP2 is an essential transcriptional repressor that mediates gene silencing through binding to methylated DNA. Binding specificity has been thought to depend on hydrophobic interactions between cytosine methyl groups and a hydrophobic patch within the methyl-CpG-binding domain (MBD). X-ray analysis of a methylated DNA-MBD cocrystal reveals, however, that the methyl groups make contact with a predominantly hydrophilic surface that includes tightly bound water molecules. This suggests that MeCP2 recognizes hydration of the major groove of methylated DNA rather than cytosine methylation per se. The MeCP2-DNA complex also identifies a unique structural role for T158, the residue most commonly mutated in Rett syndrome.