Structure-Based Identification of HDAC8 Non-histone Substrates

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

doi:10.1016/j.str.2016.02.002

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

Department of Microbiology and Molecular Genetics

Research output: Contribution to journal › Article › peer-review

45 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 language	English
Pages (from-to)	458-468
Number of pages	11
Journal	Structure
Volume	24
Issue number	3
DOIs	https://doi.org/10.1016/j.str.2016.02.002
State	Published - 1 Mar 2016

Bibliographical note

Publisher Copyright:
© 2016 Elsevier Ltd All rights reserved.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Access to Document

10.1016/j.str.2016.02.002

Cite this

@article{b052c0af01a84a02b668386cee31cc45,

title = "Structure-Based Identification of HDAC8 Non-histone Substrates",

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.",

author = "Nawsad Alam and Lior Zimmerman and Wolfson, \{Noah A.\} and Joseph, \{Caleb G.\} and Fierke, \{Carol A.\} and Ora Schueler-Furman",

year = "2016",

month = mar,

day = "1",

doi = "10.1016/j.str.2016.02.002",

language = "אנגלית",

volume = "24",

pages = "458--468",

journal = "Structure",

issn = "0969-2126",

publisher = "Cell Press",

number = "3",

}

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

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 - https://www.scopus.com/pages/publications/84959336486

U2 - 10.1016/j.str.2016.02.002

DO - 10.1016/j.str.2016.02.002

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 26933971

AN - SCOPUS:84959336486

SN - 0969-2126

VL - 24

SP - 458

EP - 468

JO - Structure

JF - Structure

IS - 3

ER -

Structure-Based Identification of HDAC8 Non-histone Substrates

Abstract

Bibliographical note

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this