5CIU: Structural Basis Of The Recognition Of H3k36me3 By Dnmt3b Pwwp Domain

DNA methylation is an important epigenetic modification involved in chromatin organization and gene expression. The function of DNA methylation depends on cell context and is correlated with histone modification patterns. In particular, trimethylation of Lys36 on histone H3 tail (H3K36me3) is associated with DNA methylation and elongation phase of transcription. PWWP domains of the de novo DNA methyltransferases DNMT3A and DNMT3B read this epigenetic mark to guide DNA methylation. Here we report the first crystal structure of the DNMT3B PWWP domain-H3K36me3 complex. Based on this structure, we propose a model of the DNMT3A PWWP domain-H3K36me3 complex and build a model of DNMT3A (PWWP-ADD-CD) in a nucleosomal context. The trimethylated side chain of Lys36 (H3K36me3) is inserted into an aromatic cage similar to the "Royal" superfamily domains known to bind methylated histones. A key interaction between trimethylated Lys36 and a conserved water molecule stabilized by Ser270 explains the lack of affinity of mutated DNMT3B (S270P) for the H3K36me3 epigenetic mark in the ICF (Immunodeficiency, Centromeric instability and Facial abnormalities) syndrome. The model of the DNMT3A-DNMT3L heterotetramer in complex with a dinucleosome highlights the mechanism for recognition of nucleosome by DNMT3s and explains the periodicity of de novo DNA methylation.
PDB ID: 5CIUDownload
MMDB ID: 137859
PDB Deposition Date: 2015/7/13
Updated in MMDB: 2016/05
Experimental Method:
x-ray diffraction
Resolution: 2.24  Å
Source Organism:
Similar Structures:
Biological Unit for 5CIU: dimeric; determined by software (PISA)
Molecular Components in 5CIU
Label Count Molecule
Proteins (2 molecules)
DNA (Cytosine-5)-methyltransferase 3B(Gene symbol: DNMT3B)
Molecule annotation
Histone H3.2
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB