5ZOO

Crystal structure of histone deacetylase 4 (HDAC4) in complex with a SMRT corepressor SP1 fragment

5ZOO の概要

• エントリーDOI: 10.2210/pdb5zoo/pdb
• 分子名称: Histone deacetylase 4, SMRT corepressor SP1 fragment, POTASSIUM ION, ... (5 entities in total)
• 機能のキーワード: protein-peptide complex, hydrolase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 45195.97

構造登録者

Park, S.Y.,Hwang, H.J.,Kim, J.S. (登録日: 2018-04-13, 公開日: 2018-11-14, 最終更新日: 2023-11-22)

主引用文献

Park, S.Y.,Kim, G.S.,Hwang, H.J.,Nam, T.H.,Park, H.S.,Song, J.,Jang, T.H.,Lee, Y.C.,Kim, J.S.
Structural basis of the specific interaction of SMRT corepressor with histone deacetylase 4.
Nucleic Acids Res., 46:11776-11788, 2018

PubMed Abstract: Modification of chromatin and related transcription factors by histone deacetylases (HDACs) is one of the major strategies for controlling gene expression in eukaryotes. The HDAC domains of class IIa HDACs repress the respective target genes by interacting with the C-terminal region of the silencing mediator for retinoid and thyroid receptor (SMRT) repression domain 3 (SRD3c). However, latent catalytic activity suggests that their roles as deacetylases in gene regulation are unclear. Here, we found that two conserved GSI-containing motifs of SRD3c are critical for HDAC4 binding. Two SMRT peptides including these motifs commonly form a β-hairpin structure in the cleft and block the catalytic entry site of HDAC4. They interact mainly with class IIa HDAC-specific residues of HDAC4 in a closed conformation. Structure-guided mutagenesis confirmed critical interactions between the SMRT peptides and HDAC4 and -5 as well as the contribution of the Arg1369 residue in the first motif for optimal binding to the two HDACs. These results indicate that SMRT binding does not activate the cryptic deacetylase activity of HDAC4 and explain how class IIa HDACs and the SMRT-HDAC3 complex are coordinated during gene regulation.

PubMed: 30321390
DOI: 10.1093/nar/gky926

実験手法

X-RAY DIFFRACTION (1.85 Å)