4UC4: Crystal Structure Of Hybrid Tudor Domain Of Human Lysine Demethylase Kdm4b

Citation:
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 A co-crystal structure of KDM4A-DTD in complex with H3K23me3 peptide reveals key intermolecular interactions for H3K23me3 recognition. Furthermore, analysis of the 2.56 A 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.
PDB ID: 4UC4Download
MMDB ID: 137393
PDB Deposition Date: 2014/8/13
Updated in MMDB: 2017/09
Experimental Method:
x-ray diffraction
Resolution: 2.56  Å
Source Organism:
Similar Structures:
Biological Unit for 4UC4: dimeric; determined by author and by software (PISA)
Molecular Components in 4UC4
Label Count Molecule
Proteins (2 molecules)
2
Lysine-specific Demethylase 4B(Gene symbol: KDM4B)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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