TY - JOUR
T1 - Structure-Based Identification of HDAC8 Non-histone Substrates
AU - Alam, Nawsad
AU - Zimmerman, Lior
AU - Wolfson, Noah A.
AU - Joseph, Caleb G.
AU - Fierke, Carol A.
AU - Schueler-Furman, Ora
N1 - Publisher Copyright:
© 2016 Elsevier Ltd All rights reserved.
PY - 2016/3/1
Y1 - 2016/3/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84959336486&partnerID=8YFLogxK
U2 - 10.1016/j.str.2016.02.002
DO - 10.1016/j.str.2016.02.002
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C2 - 26933971
AN - SCOPUS:84959336486
SN - 0969-2126
VL - 24
SP - 458
EP - 468
JO - Structure
JF - Structure
IS - 3
ER -
