6NOG

Poised-state Dot1L bound to the H2B-Ubiquitinated nucleosome

Summary for 6NOG

• Entry DOI: 10.2210/pdb6nog/pdb
• EMDB information: 0468 9384
• Descriptor: Histone H3.2, Histone H4, Histone H2A type 1, ... (8 entities in total)
• Functional Keywords: ubiquitin, nucleosome, methyltransferase, structural protein-transferase-dna complex, structural protein/transferase/dna
• Biological source: Xenopus laevis (African clawed frog); More
• Total number of polymer chains: 12
• Total formula weight: 254688.05

Authors

Worden, E.J.,Hoffmann, N.A.,Wolberger, C. (deposition date: 2019-01-16, release date: 2019-02-20, Last modification date: 2024-03-20)

Primary citation

Worden, E.J.,Hoffmann, N.A.,Hicks, C.W.,Wolberger, C.
Mechanism of Cross-talk between H2B Ubiquitination and H3 Methylation by Dot1L.
Cell, 176:1490-1501.e12, 2019

PubMed Abstract: Methylation of histone H3 K79 by Dot1L is a hallmark of actively transcribed genes that depends on monoubiquitination of H2B K120 (H2B-Ub) and is an example of histone modification cross-talk that is conserved from yeast to humans. We report here cryo-EM structures of Dot1L bound to ubiquitinated nucleosome that show how H2B-Ub stimulates Dot1L activity and reveal a role for the histone H4 tail in positioning Dot1L. We find that contacts mediated by Dot1L and the H4 tail induce a conformational change in the globular core of histone H3 that reorients K79 from an inaccessible position, thus enabling this side chain to insert into the active site in a position primed for catalysis. Our study provides a comprehensive mechanism of cross-talk between histone ubiquitination and methylation and reveals structural plasticity in histones that makes it possible for histone-modifying enzymes to access residues within the nucleosome core.

PubMed: 30765112
DOI: 10.1016/j.cell.2019.02.002

Experimental method

ELECTRON MICROSCOPY (3.9 Å)