5D6X

Crystal structure of double tudor domain of human lysine demethylase KDM4A

5D6X の概要

• エントリーDOI: 10.2210/pdb5d6x/pdb
• 関連するPDBエントリー: 5D6W 5D6Y
• 分子名称: Lysine-specific demethylase 4A, SULFATE ION (3 entities in total)
• 機能のキーワード: double tudor domain, reader domain, structural genomics, psi-2, protein structure initiative, enzyme discovery for natural product biosynthesis, natpro, oxidoreductase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 27838.51

構造登録者

Wang, F.,Su, Z.,Denu, J.M.,Phillips Jr., G.N.,Enzyme Discovery for Natural Product Biosynthesis (NatPro) (登録日: 2015-08-13, 公開日: 2015-11-25, 最終更新日: 2024-03-06)

主引用文献

Su, Z.,Wang, F.,Lee, J.H.,Stephens, K.E.,Papazyan, R.,Voronina, E.,Krautkramer, K.A.,Raman, A.,Thorpe, J.J.,Boersma, M.D.,Kuznetsov, V.I.,Miller, M.D.,Taverna, S.D.,Phillips, G.N.,Denu, J.M.
Reader domain specificity and lysine demethylase-4 family function.
Nat Commun, 7:13387-13387, 2016

PubMed Abstract: The KDM4 histone demethylases are conserved epigenetic regulators linked to development, spermatogenesis and tumorigenesis. However, how the KDM4 family targets specific chromatin regions is largely unknown. Here, an extensive histone peptide microarray analysis uncovers trimethyl-lysine histone-binding preferences among the closely related KDM4 double tudor domains (DTDs). KDM4A/B DTDs bind strongly to H3K23me3, a poorly understood histone modification recently shown to be enriched in meiotic chromatin of ciliates and nematodes. The 2.28 Å co-crystal structure of KDM4A-DTD in complex with H3K23me3 peptide reveals key intermolecular interactions for H3K23me3 recognition. Furthermore, analysis of the 2.56 Å KDM4B-DTD crystal structure pinpoints the underlying residues required for exclusive H3K23me3 specificity, an interaction supported by in vivo co-localization of KDM4B and H3K23me3 at heterochromatin in mammalian meiotic and newly postmeiotic spermatocytes. In vitro demethylation assays suggest H3K23me3 binding by KDM4B stimulates H3K36 demethylation. Together, these results provide a possible mechanism whereby H3K23me3-binding by KDM4B directs localized H3K36 demethylation during meiosis and spermatogenesis.

PubMed: 27841353
DOI: 10.1038/ncomms13387

実験手法

X-RAY DIFFRACTION (2.153 Å)