6px3

Set2 bound to nucleosomeSet2 bound to nucleosome

6px3, resolution 4.10Å Show:Asymmetric Unit Biological Assembly Structural highlights 6px3 is a 11 chain structure with sequence from Chaetomium thermophilum var. thermophilum DSM 1495, Saccharomyces cerevisiae S288C, 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 4.1Å Ligands: Experimental data: Check Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function H3C_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 36 methylation (H3K36me) is a conserved histone modification deposited by the Set2 methyltransferases. Recent findings show that over-expression or mutation of Set2 enzymes promotes cancer progression, however, mechanisms of H3K36me are poorly understood. Set2 enzymes show spurious activity on histones and histone tails, and it is unknown how they obtain specificity to methylate H3K36 on the nucleosome. In this study, we present 3.8 A cryo-EM structure of Set2 bound to the mimic of H2B ubiquitinated nucleosome. Our structure shows that Set2 makes extensive interactions with the H3 alphaN, the H3 tail, the H2A C-terminal tail and stabilizes DNA in the unwrapped conformation, which positions Set2 to specifically methylate H3K36. Moreover, we show that ubiquitin contributes to Set2 positioning on the nucleosome and stimulates the methyltransferase activity. Notably, our structure uncovers interfaces that can be targeted by small molecules for development of future cancer therapies. Nucleosome and ubiquitin position Set2 to methylate H3K36.,Bilokapic S, Halic M Nat Commun. 2019 Aug 22;10(1):3795. doi: 10.1038/s41467-019-11726-4. PMID:31439846 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Histone 3D structures Histone methyltransferase 3D structures