Structure-Based Identification of HDAC8 Non-histone Substrates

被引：40

作者：

Alam, Nawsad ^{[1
]}

Zimmerman, Lior ^{[1
]}

Wolfson, Noah A. ^{[2
]}

Joseph, Caleb G. ^{[3
]}

Fierke, Carol A. ^{[2
,3
,4
]}

Schueler-Furman, Ora ^{[1
]}

机构：

[1] Hebrew Univ Jerusalem, Fac Med, Inst Med Res Israel Canada, Dept Microbiol & Mol Genet, IL-91120 Jerusalem, Israel

[2] Univ Michigan, Dept Biol Chem, Ann Arbor, MI 48109 USA

[3] Univ Michigan, Dept Med Chem, Ann Arbor, MI 48109 USA

[4] Univ Michigan, Dept Chem, Ann Arbor, MI 48109 USA

来源：

STRUCTURE | 2016年 / 24卷 / 03期

基金：

以色列科学基金会; 美国国家卫生研究院; 欧洲研究理事会;

关键词：

HISTONE DEACETYLASE 8; LYSINE DEACETYLASES; PROTEIN PHOSPHATASE; PEPTIDE ARRAYS; ACETYLATION; SPECIFICITY; COMPLEXES; BINDING; FAMILY; ALPHA;

D O I：

10.1016/j.str.2016.02.002

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

HDAC8 is a member of the family of histone deacetylases (HDACs) that catalyze the deacetylation of acetyl lysine residues within histone and non-histone proteins. The recent identification of novel non-histone HDAC8 substrates such as SMC3, ERR alpha, and ARID1A indicates a complex functionality of this enzyme in cellular homeostasis. To discover additional HDAC8 substrates, we developed a comprehensive, structure-based approach based on Rosetta FlexPepBind, a protocol that evaluates peptide-binding ability to a receptor from structural models of this interaction. Here we adapt this protocol to identify HDAC8 substrates using peptide sequences extracted from proteins with known acetylated sites. The many new in vitro HDAC8 peptide substrates identified in this study suggest that numerous cellular proteins are HDAC8 substrates, thus expanding our view of the acetylome and its regulation by HDAC8.

引用

页码：458 / 468

页数：11

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