Structural Basis for Hydroxymethylcytosine Recognition by the SRA Domain of UHRF2, Molecular Cell, Available online 8 May 2014
发布时间：2014年05月12日
Molecular Cell, Available online 8 May 2014, http://dx.doi.org/10.1016/j.molcel.2014.04.003
Structural Basis for Hydroxymethylcytosine Recognition by the SRA Domain of UHRF2
Ting Zhou1, 2, Jun Xiong3, Mingzhu Wang1, Na Yang1, Jiemin Wong4, Bing Zhu3, Rui-Ming Xu1
Summary
Methylated cytosine of CpG dinucleotides in vertebrates may be oxidized by Tet proteins, a process that can lead to DNA demethylation. The predominant oxidation product, 5-hydroxymethylcytosine (5hmC), has been implicated in embryogenesis, cell differentiation, and human diseases. Recently, the SRA domain of UHRF2 (UHRF2-SRA) has been reported to specifically recognize 5hmC, but how UHRF2 recognizes this modification is unclear. Here we report the structure of UHRF2-SRA in complex with a 5hmC-containing DNA. The structure reveals that the conformation of a phenylalanine allows the formation of an optimal 5hmC binding pocket, and a hydrogen bond between the hydroxyl group of 5hmC and UHRF2-SRA is critical for their preferential binding. Further structural and biochemical analyses unveiled the role of SRA domains as a versatile reader of modified DNA, and the knowledge should facilitate further understanding of the biological function of UHRF2 and the comprehension of DNA hydroxymethylation in general.
附件下载：
Structural Basis for Hydroxymethylcytosine Recognition by the SRA Domain of UHRF2, Molecular Cell, Available online 8 May 2014
Molecular Cell, Available online 8 May 2014, http://dx.doi.org/10.1016/j.molcel.2014.04.003
Structural Basis for Hydroxymethylcytosine Recognition by the SRA Domain of UHRF2
Ting Zhou1, 2, Jun Xiong3, Mingzhu Wang1, Na Yang1, Jiemin Wong4, Bing Zhu3, Rui-Ming Xu1
Summary
Methylated cytosine of CpG dinucleotides in vertebrates may be oxidized by Tet proteins, a process that can lead to DNA demethylation. The predominant oxidation product, 5-hydroxymethylcytosine (5hmC), has been implicated in embryogenesis, cell differentiation, and human diseases. Recently, the SRA domain of UHRF2 (UHRF2-SRA) has been reported to specifically recognize 5hmC, but how UHRF2 recognizes this modification is unclear. Here we report the structure of UHRF2-SRA in complex with a 5hmC-containing DNA. The structure reveals that the conformation of a phenylalanine allows the formation of an optimal 5hmC binding pocket, and a hydrogen bond between the hydroxyl group of 5hmC and UHRF2-SRA is critical for their preferential binding. Further structural and biochemical analyses unveiled the role of SRA domains as a versatile reader of modified DNA, and the knowledge should facilitate further understanding of the biological function of UHRF2 and the comprehension of DNA hydroxymethylation in general.
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文章链接：http://dx.doi.org/10.1016/j.molcel.2014.04.003