Mechanism of assembly, activation and lysine selection by the SIN3B histone deacetylase complex.
Date
2023-05-03Author
Wan, MSM
Muhammad, R
Koliopoulos, MG
Roumeliotis, TI
Choudhary, JS
Alfieri, C
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
Humans
Histones
Lysine
Protein Processing, Post-Translational
Saccharomyces cerevisiae
Histone Deacetylases
Acetylation
Histone Deacetylase 1
Repressor Proteins
Research team
Mol mech cell cycle reg
Functional Proteomics
Prote & Metabolomics Fac
Language
eng
Date accepted
2023-04-22
License start date
2023-05-03
Citation
Nature Communications, 2023, 14 (1), pp. 2556 -
Publisher
NATURE PORTFOLIO