6NZO
Set2 bound to nucleosome
Summary for 6NZO
| Entry DOI | 10.2210/pdb6nzo/pdb |
| EMDB information | 0559 |
| Descriptor | Histone H3, Histone H4, Ubiquitin-60S ribosomal protein L40,Histone H2A, ... (8 entities in total) |
| Functional Keywords | set2, nucleosome, chromatin, kmt, gene regulation |
| Biological source | Xenopus laevis (African clawed frog) More |
| Total number of polymer chains | 11 |
| Total formula weight | 326674.62 |
| Authors | Halic, M.,Bilokapic, S. (deposition date: 2019-02-14, release date: 2019-08-28, Last modification date: 2019-09-04) |
| Primary citation | Bilokapic, S.,Halic, M. Nucleosome and ubiquitin position Set2 to methylate H3K36. Nat Commun, 10:3795-3795, 2019 Cited by PubMed Abstract: 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 Å cryo-EM structure of Set2 bound to the mimic of H2B ubiquitinated nucleosome. Our structure shows that Set2 makes extensive interactions with the H3 αN, 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. PubMed: 31439846DOI: 10.1038/s41467-019-11726-4 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.8 Å) |
Structure validation
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