6nj9

Active state Dot1L bound to the H2B-Ubiquitinated nucleosome, 2-to-1 complex

Loading... Status: waiting for Mol* initialization Structural highlights 6nj9 is a 14 chain structure with sequence from Homo sapiens, Xenopus laevis and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.96Å Ligands: NLE, SAM Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed 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. Mechanism of Cross-talk between H2B Ubiquitination and H3 Methylation by Dot1L.,Worden EJ, Hoffmann NA, Hicks CW, Wolberger C Cell. 2019 Feb 8. pii: S0092-8674(19)30151-5. doi: 10.1016/j.cell.2019.02.002. PMID:30765112 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Histone 3D structures Histone methyltransferase 3D structures

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