8OF4
Nucleosome Bound human SIRT6 (Composite)
Summary for 8OF4
| Entry DOI | 10.2210/pdb8of4/pdb |
| EMDB information | 16842 16843 16845 16861 |
| Descriptor | Histone H3.2, Histone H4, Histone H2A type 1, ... (8 entities in total) |
| Functional Keywords | transferase, deacetylase, histone h3 deacetylation, gene regulation |
| Biological source | Xenopus laevis (African clawed frog) More |
| Total number of polymer chains | 11 |
| Total formula weight | 238534.87 |
| Authors | Smirnova, E.,Bignon, E.,Schultz, P.,Papai, G.,Ben-Shem, A. (deposition date: 2023-03-13, release date: 2023-08-09, Last modification date: 2024-03-13) |
| Primary citation | Smirnova, E.,Bignon, E.,Schultz, P.,Papai, G.,Ben Shem, A. Binding to nucleosome poises human SIRT6 for histone H3 deacetylation. Elife, 12:-, 2024 Cited by PubMed Abstract: Sirtuin 6 (SIRT6) is an NAD-dependent histone H3 deacetylase that is prominently found associated with chromatin, attenuates transcriptionally active promoters and regulates DNA repair, metabolic homeostasis and lifespan. Unlike other sirtuins, it has low affinity to free histone tails but demonstrates strong binding to nucleosomes. It is poorly understood how SIRT6 docking on nucleosomes stimulates its histone deacetylation activity. Here, we present the structure of human SIRT6 bound to a nucleosome determined by cryogenic electron microscopy. The zinc finger domain of SIRT6 associates tightly with the acidic patch of the nucleosome through multiple arginine anchors. The Rossmann fold domain binds to the terminus of the looser DNA half of the nucleosome, detaching two turns of the DNA from the histone octamer and placing the NAD binding pocket close to the DNA exit site. This domain shows flexibility with respect to the fixed zinc finger and moves with, but also relative to, the unwrapped DNA terminus. We apply molecular dynamics simulations of the histone tails in the nucleosome to show that in this mode of interaction, the active site of SIRT6 is perfectly poised to catalyze deacetylation of the H3 histone tail and that the partial unwrapping of the DNA allows even lysines close to the H3 core to reach the enzyme. PubMed: 38415718DOI: 10.7554/eLife.87989 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.94 Å) |
Structure validation
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