6nn6

Structure of Dot1L-H2BK120ub nucleosome complexStructure of Dot1L-H2BK120ub nucleosome complex

6nn6, resolution 3.90Å Show:Asymmetric Unit Biological Assembly Structural highlights 6nn6 is a 12 chain structure with sequence from African clawed frog and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Gene: DOT1L, KIAA1814, KMT4 (HUMAN), UBC (HUMAN) Activity: Histone-lysine N-methyltransferase, with EC number 2.1.1.43 Experimental data: Check Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [H2A1_XENLA] Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. [DOT1L_HUMAN] Histone methyltransferase. Methylates 'Lys-79' of histone H3. Nucleosomes are preferred as substrate compared to free histones. Binds to DNA. [H4_XENLA] Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. [H32_XENLA] Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. [H2B11_XENLA] Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. Publication Abstract from PubMed Histone H3 lysine 79 (H3K79) methylation is enriched on actively transcribed genes, and its misregulation is a hallmark of leukemia. Methylation of H3K79, which resides on the structured disk face of the nucleosome, is mediated by the Dot1L methyltransferase. Dot1L activity is part of a trans-histone crosstalk pathway, requiring prior histone H2B ubiquitylation of lysine 120 (H2BK120ub) for optimal activity. However, the molecular details describing both how Dot1L binds to the nucleosome and why Dot1L is activated by H2BK120 ubiquitylation are unknown. Here, we present the cryoelectron microscopy (cryo-EM) structure of Dot1L bound to a nucleosome reconstituted with site-specifically ubiquitylated H2BK120. The structure reveals that Dot1L engages the nucleosome acidic patch using a variant arginine anchor and occupies a conformation poised for methylation. In this conformation, Dot1L and ubiquitin interact directly through complementary hydrophobic surfaces. This study establishes a path to better understand Dot1L function in normal and leukemia cells. Structural Basis for Recognition of Ubiquitylated Nucleosome by Dot1L Methyltransferase.,Anderson CJ, Baird MR, Hsu A, Barbour EH, Koyama Y, Borgnia MJ, McGinty RK Cell Rep. 2019 Feb 12;26(7):1681-1690.e5. doi: 10.1016/j.celrep.2019.01.058. PMID:30759380 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Histone 3D structures Histone methyltransferase 3D structures