IHEP OpenIR  > 多学科研究中心
Structural insight into substrate preference for TET- mediated oxidation
Hu, LL; Lu, JY; Cheng, JD; Rao, QH; Li, Z; Hou, HF; Lou, ZY; Zhang, L; Li, W; Gong, W; Liu, MJ; Sun, C; Yin, XT; Li, J; Tan, XS; Wang, PC; Wang, YS; Fang, D; Cui, Q; Yang, PY; He, C; Jiang, HL; Luo, C; Xu, YH; Hou HF(侯海峰)
2015
发表期刊NATURE
卷号527期号:7576页码:118-122
文章类型Article
摘要DNA methylation is an important epigenetic modification(1-3). Ten-eleven translocation (TET) proteins are involved in DNA demethylation through iteratively oxidizing 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC)(4-8). Here we show that human TET1 and TET2 are more active on 5mC-DNA than 5hmC/5fC-DNA substrates. We determine the crystal structures of TET2-5hmC-DNA and TET2-5fC-DNA complexes at 1.80 angstrom and 1.97 angstrom resolution, respectively. The cytosine portion of 5hmC/5fC is specifically recognized by TET2 in a manner similar to that of 5mC in the TET2-5mC-DNA structure(9), and the pyrimidine base of 5mC/5hmC/5fC adopts an almost identical conformation within the catalytic cavity. However, the hydroxyl group of 5hmC and carbonyl group of 5fC face towards the opposite direction because the hydroxymethyl group of 5hmC and formyl group of 5fC adopt restrained conformations through forming hydrogen bonds with the 1-carboxylate of NOG and N4 exocyclic nitrogen of cytosine, respectively. Biochemical analyses indicate that the substrate preference of TET2 results from the different efficiencies of hydrogen abstraction in TET2-mediated oxidation. The restrained conformation of 5hmC and 5fC within the catalytic cavity may prevent their abstractable hydrogen(s) adopting a favourable orientation for hydrogen abstraction and thus result in low catalytic efficiency. Our studies demonstrate that the substrate preference of TET2 results from the intrinsic value of its substrates at their 5mC derivative groups and suggest that 5hmC is relatively stable and less prone to further oxidation by TET proteins. Therefore, TET proteins are evolutionarily tuned to be less reactive towards 5hmC and facilitate the generation of 5hmC as a potentially stable mark for regulatory functions.
学科领域Science & Technology - Other Topics
DOI10.1038/nature15713
收录类别SCI
WOS类目Multidisciplinary Sciences
WOS记录号WOS:000364270700055
引用统计
被引频次:54[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.ihep.ac.cn/handle/311005/228828
专题多学科研究中心
推荐引用方式
GB/T 7714
Hu, LL,Lu, JY,Cheng, JD,et al. Structural insight into substrate preference for TET- mediated oxidation[J]. NATURE,2015,527(7576):118-122.
APA Hu, LL.,Lu, JY.,Cheng, JD.,Rao, QH.,Li, Z.,...&侯海峰.(2015).Structural insight into substrate preference for TET- mediated oxidation.NATURE,527(7576),118-122.
MLA Hu, LL,et al."Structural insight into substrate preference for TET- mediated oxidation".NATURE 527.7576(2015):118-122.
条目包含的文件
文件名称/大小 文献类型 版本类型 开放类型 使用许可
777.pdf(8243KB)期刊论文作者接受稿限制开放CC BY-NC-SA请求全文
个性服务
推荐该条目
保存到收藏夹
查看访问统计
导出为Endnote文件
谷歌学术
谷歌学术中相似的文章
[Hu, LL]的文章
[Lu, JY]的文章
[Cheng, JD]的文章
百度学术
百度学术中相似的文章
[Hu, LL]的文章
[Lu, JY]的文章
[Cheng, JD]的文章
必应学术
必应学术中相似的文章
[Hu, LL]的文章
[Lu, JY]的文章
[Cheng, JD]的文章
相关权益政策
暂无数据
收藏/分享
所有评论 (0)
暂无评论
 

除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。