8BPB

Cryo-EM structure of the human SIN3B histone deacetylase core complex at 2.8 Angstrom

8BPB の概要

• エントリーDOI: 10.2210/pdb8bpb/pdb
• EMDBエントリー: 16148
• 分子名称: Isoform 2 of Paired amphipathic helix protein Sin3b, Histone deacetylase 2, PHD finger protein 12, ... (7 entities in total)
• 機能のキーワード: hdac, chromatin, cell cycle, transcription, gene regulation
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 226582.77

構造登録者

Wan, M.S.M.,Muhammad, R.,Koliopolous, M.G.,Alfieri, C. (登録日: 2022-11-16, 公開日: 2023-05-10, 最終更新日: 2024-03-27)

主引用文献

Wan, M.S.M.,Muhammad, R.,Koliopoulos, M.G.,Roumeliotis, T.I.,Choudhary, J.S.,Alfieri, C.
Mechanism of assembly, activation and lysine selection by the SIN3B histone deacetylase complex.
Nat Commun, 14:2556-2556, 2023

PubMed Abstract: Lysine acetylation in histone tails is a key post-translational modification that controls transcription activation. Histone deacetylase complexes remove histone acetylation, thereby repressing transcription and regulating the transcriptional output of each gene. Although these complexes are drug targets and crucial regulators of organismal physiology, their structure and mechanisms of action are largely unclear. Here, we present the structure of a complete human SIN3B histone deacetylase holo-complex with and without a substrate mimic. Remarkably, SIN3B encircles the deacetylase and contacts its allosteric basic patch thereby stimulating catalysis. A SIN3B loop inserts into the catalytic tunnel, rearranges to accommodate the acetyl-lysine moiety, and stabilises the substrate for specific deacetylation, which is guided by a substrate receptor subunit. Our findings provide a model of specificity for a main transcriptional regulator conserved from yeast to human and a resource of protein-protein interactions for future drug designs.

PubMed: 37137925
DOI: 10.1038/s41467-023-38276-0

実験手法

ELECTRON MICROSCOPY (2.8 Å)