SNAP output for PDB entry 6jma [SNAP web server]

PDB-id

6jma; SNAP-derived features in text and JSON formats; DNAproDB

Class

gene regulation

Method

cryo-EM (6.8 Å)

Summary

cryo-EM structure of dot1l bound to h2b ubiquitinated nucleosome

Reference

Jang S, Kang C, Yang HS, Jung T, Hebert H, Chung KY, Kim SJ, Hohng S, Song JJ (2019): "Structural basis of recognition and destabilization of the histone H2B ubiquitinated nucleosome by the DOT1L histone H3 Lys79 methyltransferase." Genes Dev., 33, 620-625. doi: 10.1101/gad.323790.118.

Abstract

DOT1L is a histone H3 Lys79 methyltransferase whose activity is stimulated by histone H2B Lys120 ubiquitination, suggesting cross-talk between histone H3 methylation and H2B ubiquitination. Here, we present cryo-EM structures of DOT1L complexes with unmodified or H2B ubiquitinated nucleosomes, showing that DOT1L recognizes H2B ubiquitin and the H2A/H2B acidic patch through a C-terminal hydrophobic helix and an arginine anchor in DOT1L, respectively. Furthermore, the structures combined with single-molecule FRET experiments show that H2B ubiquitination enhances a noncatalytic function of the DOT1L-destabilizing nucleosome. These results establish the molecular basis of the cross-talk between H2B ubiquitination and H3 Lys79 methylation as well as nucleosome destabilization by DOT1L.