Molecular mechanism for vitamin C-derived C-5-glyceryl-methylcytosine DNA modification catalyzed by algal TET homologue CMD1

doi:10.1038/s41467-021-21061-2

	Molecular mechanism for vitamin C-derived C-5-glyceryl-methylcytosine DNA modification catalyzed by algal TET homologue CMD1
	Li, Wenjing 1; Zhang, Tianlong 1; Sun, Mingliang 1; Shi, Yu1,2 ; Zhang, Xiao-Jie 1; Xu, Guo-Liang 1; Ding, Jianping1,2,3
	2021-02-02
发表期刊	NATURE COMMUNICATIONS (IF:14.7[JCR-2023],16.1[5-Year])
ISSN	2041-1723
卷号	12 期号:1 页码:#VALUE!
DOI	10.1038/s41467-021-21061-2
摘要	C-5-glyceryl-methylcytosine (5gmC) is a novel DNA modification catalyzed by algal TET homologue CMD1 using vitamin C (VC) as co-substrate. Here, we report the structures of CMD1 in apo form and in complexes with VC or/and dsDNA. CMD1 exhibits comparable binding affinities for DNAs of different lengths, structures, and 5mC levels, and displays a moderate substrate preference for 5mCpG-containing DNA. CMD1 adopts the typical DSBH fold of Fe2+/2-OG-dependent dioxygenases. The lactone form of VC binds to the active site and mono-coordinates the Fe2+ in a manner different from 2-OG. The dsDNA binds to a positively charged cleft of CMD1 and the 5mC/C is inserted into the active site and recognized by CMD1 in a similar manner as the TET proteins. The functions of key residues are validated by mutagenesis and activity assay. Our structural and biochemical data together reveal the molecular mechanism for the VC-derived 5gmC DNA modification by CMD1. C-5-glyceryl-methylcytosine is a DNA modification that plays a role in the regulation of green alga photosynthesis and is catalysed by CMD1, using vitamin C (VC) as a co-substrate. Here, the authors provide insights into the catalytic mechanism of CMD1 by determining the crystal structures of apo CMD1 and CMD1 bound to either VC or DNA, as well as the ternary CMD1/VC/DNA complex structure.
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收录类别	SCI ; SCIE
语种	英语
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000617063000014
出版者	NATURE RESEARCH
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/125826
专题	生命科学与技术学院_硕士生生命科学与技术学院_特聘教授组_丁建平组生命科学与技术学院_博士生
通讯作者	Ding, Jianping
作者单位	1.Univ Chinese Acad Sci, Chinese Acad Sci, Ctr Excellence Mol Cell Sci, State Key Lab Mol Biol,Shanghai Inst Biochem & Ce, Shanghai, Peoples R China; 2.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China; 3.Univ Chinese Acad Sci, Sch Life Sci, Hangzhou Inst Adv Study, Hangzhou, Peoples R China
通讯作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Li, Wenjing,Zhang, Tianlong,Sun, Mingliang,et al. Molecular mechanism for vitamin C-derived C-5-glyceryl-methylcytosine DNA modification catalyzed by algal TET homologue CMD1[J]. NATURE COMMUNICATIONS,2021,12(1):#VALUE!.
APA	Li, Wenjing.,Zhang, Tianlong.,Sun, Mingliang.,Shi, Yu.,Zhang, Xiao-Jie.,...&Ding, Jianping.(2021).Molecular mechanism for vitamin C-derived C-5-glyceryl-methylcytosine DNA modification catalyzed by algal TET homologue CMD1.NATURE COMMUNICATIONS,12(1),#VALUE!.
MLA	Li, Wenjing,et al."Molecular mechanism for vitamin C-derived C-5-glyceryl-methylcytosine DNA modification catalyzed by algal TET homologue CMD1".NATURE COMMUNICATIONS 12.1(2021):#VALUE!.