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-Structure paper
タイトル | Structural Basis of Sirtuin 6-Catalyzed Nucleosome Deacetylation. |
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ジャーナル・号・ページ | J Am Chem Soc, Vol. 145, Issue 12, Page 6811-6822, Year 2023 |
掲載日 | 2023年3月29日 |
著者 | Zhipeng A Wang / Jonathan W Markert / Samuel D Whedon / Maheeshi Yapa Abeywardana / Kwangwoon Lee / Hanjie Jiang / Carolay Suarez / Hening Lin / Lucas Farnung / Philip A Cole / |
PubMed 要旨 | The reversible acetylation of histone lysine residues is controlled by the action of acetyltransferases and deacetylases (HDACs), which regulate chromatin structure and gene expression. The sirtuins ...The reversible acetylation of histone lysine residues is controlled by the action of acetyltransferases and deacetylases (HDACs), which regulate chromatin structure and gene expression. The sirtuins are a family of NAD-dependent HDAC enzymes, and one member, sirtuin 6 (Sirt6), influences DNA repair, transcription, and aging. Here, we demonstrate that Sirt6 is efficient at deacetylating several histone H3 acetylation sites, including its canonical site Lys9, in the context of nucleosomes but not free acetylated histone H3 protein substrates. By installing a chemical warhead at the Lys9 position of histone H3, we trap a catalytically poised Sirt6 in complex with a nucleosome and employ this in cryo-EM structural analysis. The structure of Sirt6 bound to a nucleosome reveals extensive interactions between distinct segments of Sirt6 and the H2A/H2B acidic patch and nucleosomal DNA, which accounts for the rapid deacetylation of nucleosomal H3 sites and the disfavoring of histone H2B acetylation sites. These findings provide a new framework for understanding how HDACs target and regulate chromatin. |
リンク | J Am Chem Soc / PubMed:36930461 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.1 Å |
構造データ | EMDB-28915, PDB-8f86: |
化合物 | ChemComp-ZSL: ChemComp-ZN: |
由来 |
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キーワード | GENE REGULATION / nucleosome / SIRTUIN6 / histone deacylation / H3K9Ac |