Structure-Based Identification of HDAC8 Non-histone Substrates

Nawsad Alam, Lior Zimmerman, Noah A. Wolfson, Caleb G. Joseph, Carol A. Fierke, Ora Schueler-Furman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

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, ERRα, 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.

Original languageAmerican English
Pages (from-to)458-468
Number of pages11
JournalStructure
Volume24
Issue number3
DOIs
StatePublished - 1 Mar 2016

Bibliographical note

Publisher Copyright:
© 2016 Elsevier Ltd All rights reserved.

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