IHEP OpenIR
Structure-function analysis reveals a novel mechanism for regulation of histone demethylase LSD2/AOF1/KDM1b
Zhang, Q; Qi, SK; Xu, MC; Yu, L; Tao, Y; Deng, ZQ; Wu, W; Li, JW; Chen, ZZ; Wong, JM;陶冶
2013
Source PublicationCELL RESEARCH
ISSN1001-0602
Volume23Issue:2Pages:225-241
AbstractLSD2/A0F1/KDM1b catalyzes demethylation of mono- and di-methylated H3K4 and plays an important role in transcriptional regulation and genomic imprinting. Here, we report the high-resolution crystal structures of apo-LSD2 and LSD2 in complex with a peptide that mimics H3K4me2. Three structural domains of LSD2, namely, the novel N-terminal zinc finger, the centrally located SWIRM domain, and the C-terminal oxidase domain, closely pack together to form a boot-shaped structure. The active site cavity in the oxidase domain is large enough to accommodate several residues of the histone H3 tail and cannot discriminate between the different states of H3K4 methylation. The N-terminal zinc-finger domain, composed of a novel C4H2C2-type zinc finger and a specific CW-type zinc finger, is required for demethylase activity and, surprisingly, the binding of cofactor flavin adenine dinucleotide (FAD). In fact, a relay of extensive interactions through the zinc finger-SWIRM-oxidase domains is required for LSD2 demethylase activity and the binding of FAD. These results reveal a novel mechanism for the zinc finger and SWIRM domains in controlling LSD2 demethylase activity and provide a framework for elucidating the regulation and function of LSD2.
KeywordLSD2 complex structures C4H2C2 zinc finger CW zinc finger SWIRM FAD amine oxidase
Subject AreaCell Biology
DOI10.1038/cr.2012.177
Indexed BySCI
Language英语
WOS IDWOS:000315426400011
Citation statistics
Document Type期刊论文
Identifierhttp://ir.ihep.ac.cn/handle/311005/223898
Collection中国科学院高能物理研究所
Recommended Citation
GB/T 7714
Zhang, Q,Qi, SK,Xu, MC,et al. Structure-function analysis reveals a novel mechanism for regulation of histone demethylase LSD2/AOF1/KDM1b[J]. CELL RESEARCH,2013,23(2):225-241.
APA Zhang, Q.,Qi, SK.,Xu, MC.,Yu, L.,Tao, Y.,...&Wong, JM;陶冶.(2013).Structure-function analysis reveals a novel mechanism for regulation of histone demethylase LSD2/AOF1/KDM1b.CELL RESEARCH,23(2),225-241.
MLA Zhang, Q,et al."Structure-function analysis reveals a novel mechanism for regulation of histone demethylase LSD2/AOF1/KDM1b".CELL RESEARCH 23.2(2013):225-241.
Files in This Item:
File Name/Size DocType Version Access License
2401.pdf(1690KB)期刊论文作者接受稿开放获取CC BY-NC-SAApplication Full Text
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[Zhang, Q]'s Articles
[Qi, SK]'s Articles
[Xu, MC]'s Articles
Baidu academic
Similar articles in Baidu academic
[Zhang, Q]'s Articles
[Qi, SK]'s Articles
[Xu, MC]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Zhang, Q]'s Articles
[Qi, SK]'s Articles
[Xu, MC]'s Articles
Terms of Use
No data!
Social Bookmark/Share
All comments (0)
No comment.
 

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.