Mechanism of assembly, activation and lysine selection by the SIN3B histone deacetylase complex.
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Authors
Wan, MSM
Muhammad, R
Koliopoulos, MG
Roumeliotis, TI
Choudhary, JS
Alfieri, C
Muhammad, R
Koliopoulos, MG
Roumeliotis, TI
Choudhary, JS
Alfieri, C
Document Type
Journal Article
Date
2023-05-03
Date Accepted
2023-04-22
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.
Citation
Nature Communications, 2023, 14 (1), pp. 2556 -
Source Title
Nature Communications
Publisher
NATURE PORTFOLIO
ISSN
2041-1723
eISSN
2041-1723
2041-1723
2041-1723
Collections
Research Team
Mol mech cell cycle reg
Functional Proteomics
Prote & Metabolomics Fac
Functional Proteomics
Prote & Metabolomics Fac