3N9Q

ceKDM7A from C.elegans, complex with H3K4me3 peptide, H3K27me2 peptide and NOG

3N9Q の概要

• エントリーDOI: 10.2210/pdb3n9q/pdb
• 関連するPDBエントリー: 3N9L 3N9M 3N9N 3N9O 3N9P
• 分子名称: Putative uncharacterized protein, Histone H3 peptide, FE (II) ION, ... (7 entities in total)
• 機能のキーワード: histone, methylation, demethylase, phd, jmjc, fe(ii) and alpha-kg (alpha-ketoglutarate)-dependent dioxygenase family, oxidoreductase
• 由来する生物種: Caenorhabditis elegans; 詳細
• 細胞内の位置: Nucleus: Q9GYI0 P08898 P08898
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 65530.02

構造登録者

Yang, Y.,Hu, L.,Wang, P.,Hou, H.,Chen, C.D.,Xu, Y. (登録日: 2010-05-31, 公開日: 2010-06-30, 最終更新日: 2023-11-01)

主引用文献

Yang, Y.,Hu, L.,Wang, P.,Hou, H.,Lin, Y.,Liu, Y.,Li, Z.,Gong, R.,Feng, X.,Zhou, L.,Zhang, W.,Dong, Y.,Yang, H.,Lin, H.,Wang, Y.,Chen, C.D.,Xu, Y.
Structural insights into a dual-specificity histone demethylase ceKDM7A from Caenorhabditis elegans
Cell Res., 20:886-898, 2010

PubMed Abstract: Histone lysine methylation can be removed by JmjC domain-containing proteins in a sequence- and methylation-state-specific manner. However, how substrate specificity is determined and how the enzymes are regulated were largely unknown. We recently found that ceKDM7A, a PHD- and JmjC domain-containing protein, is a histone demethylase specific for H3K9me2 and H3K27me2, and the PHD finger binding to H3K4me3 guides the demethylation activity in vivo. To provide structural insight into the molecular mechanisms for the enzymatic activity and the function of the PHD finger, we solved six crystal structures of the enzyme in apo form and in complex with single or two peptides containing various combinations of H3K4me3, H3K9me2, and H3K27me2 modifications. The structures indicate that H3K9me2 and H3K27me2 interact with ceKDM7A in a similar fashion, and that the peptide-binding specificity is determined by a network of specific interactions. The geometrical measurement of the structures also revealed that H3K4me3 associated with the PHD finger and H3K9me2 bound to the JmjC domain are from two separate molecules, suggesting a trans-histone peptide-binding mechanism. Thus, our systemic structural studies reveal not only the substrate recognition by the catalytic domain but also more importantly, the molecular mechanism of dual specificity of ceDKM7A for both H3K9me2 and H3K27me2.

PubMed: 20567261
DOI: 10.1038/cr.2010.86

実験手法

X-RAY DIFFRACTION (2.3 Å)