Structure-function analysis reveals a novel mechanism for regulation of histone demethylase LSD2/AOF1/KDM1b
文献类型：期刊论文
| 作者 | Zhang, Q; Qi, SK; Xu, MC; Yu, L; Tao, Y; Deng, ZQ; Wu, W; Li, JW; Chen, ZZ; Wong, JM;陶冶
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| 刊名 | CELL RESEARCH
 |
| 出版日期 | 2013 |
| 卷号 | 23期号:2页码:225-241 |
| 关键词 | LSD2 complex structures C4H2C2 zinc finger CW zinc finger SWIRM FAD amine oxidase |
| ISSN号 | 1001-0602 |
| DOI | 10.1038/cr.2012.177 |
| 英文摘要 | LSD2/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. |
| 学科主题 | Cell Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000315426400011 |
| 源URL | [http://ir.ihep.ac.cn/handle/311005/223898]  |
| 专题 | 中国科学院高能物理研究所 |
| 推荐引用方式 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. |
入库方式： OAI收割
来源：高能物理研究所
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