8OF4

Nucleosome Bound human SIRT6 (Composite)

8OF4 の概要

• エントリーDOI: 10.2210/pdb8of4/pdb
• EMDBエントリー: 16842 16843 16845 16861
• 分子名称: Histone H3.2, Histone H4, Histone H2A type 1, ... (8 entities in total)
• 機能のキーワード: transferase, deacetylase, histone h3 deacetylation, gene regulation
• 由来する生物種: Xenopus laevis (African clawed frog); 詳細
• タンパク質・核酸の鎖数: 11
• 化学式量合計: 238534.87

構造登録者

Smirnova, E.,Bignon, E.,Schultz, P.,Papai, G.,Ben-Shem, A. (登録日: 2023-03-13, 公開日: 2023-08-09, 最終更新日: 2024-03-13)

主引用文献

Smirnova, E.,Bignon, E.,Schultz, P.,Papai, G.,Ben Shem, A.
Binding to nucleosome poises human SIRT6 for histone H3 deacetylation.
Elife, 12:-, 2024

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: 38415718
DOI: 10.7554/eLife.87989

実験手法

ELECTRON MICROSCOPY (2.94 Å)