The NuA4 Core Complex Acetylates Nucleosomal Histone H4 through a Double Recognition Mechanism

Peng Xu; Chengmin Li; Zhihong Chen; Shuanying Jiang; Shilong Fan; Jiawei Wang; Junbiao Dai; Ping Zhu; Zhucheng Chen

doi:10.1016/j.molcel.2016.07.024

The NuA4 Core Complex Acetylates Nucleosomal Histone H4 through a Double Recognition Mechanism

Mol Cell. 2016 Sep 15;63(6):965-75. doi: 10.1016/j.molcel.2016.07.024. Epub 2016 Sep 1.

Authors

Peng Xu¹, Chengmin Li², Zhihong Chen¹, Shuanying Jiang³, Shilong Fan³, Jiawei Wang⁴, Junbiao Dai³, Ping Zhu⁵, Zhucheng Chen⁶

Affiliations

¹ MOE Key Laboratory of Protein Science, Tsinghua University, Beijing 100086, China; School of Life Science, Tsinghua University, Beijing 100086, China.
² National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
³ School of Life Science, Tsinghua University, Beijing 100086, China.
⁴ State Key Laboratory of Bio-membrane and Membrane Biotechnology, Tsinghua University, Beijing 100086, China.
⁵ National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: [email protected].
⁶ MOE Key Laboratory of Protein Science, Tsinghua University, Beijing 100086, China; School of Life Science, Tsinghua University, Beijing 100086, China. Electronic address: [email protected].

PMID: 27594449
DOI: 10.1016/j.molcel.2016.07.024

Abstract

NuA4 catalyzes the acetylation of nucleosomes at histone H4, which is a well-established epigenetic event, controlling many genomic processes in Saccharomyces cerevisiae. Here we report the crystal structures of the NuA4 core complex and a cryoelectron microscopy structure with the nucleosome. The structures show that the histone-binding pocket of the enzyme is rearranged, suggesting its activation. The enzyme binds the histone tail mainly through the target lysine residue, with a preference for a small residue at the -1 position. The complex engages the nucleosome at the dish face and orients its catalytic pocket close to the H4 tail to achieve selective acetylation. The combined data reveal a space-sequence double recognition mechanism of the histone tails by a modifying enzyme in the context of the nucleosome.

MeSH terms

Acetylation
Amino Acid Sequence
Catalytic Domain
Cloning, Molecular
Cryoelectron Microscopy
Crystallography, X-Ray
Escherichia coli / genetics
Escherichia coli / metabolism
Gene Expression
Histone Acetyltransferases / chemistry*
Histone Acetyltransferases / genetics
Histone Acetyltransferases / metabolism
Histones / chemistry*
Histones / genetics
Histones / metabolism
Lysine / chemistry
Lysine / metabolism
Molecular Docking Simulation
Nucleosomes / chemistry
Nucleosomes / metabolism
Protein Binding
Protein Interaction Domains and Motifs
Protein Processing, Post-Translational*
Protein Structure, Secondary
Recombinant Proteins / chemistry
Recombinant Proteins / genetics
Recombinant Proteins / metabolism
Saccharomyces cerevisiae / enzymology*
Saccharomyces cerevisiae / genetics
Saccharomyces cerevisiae Proteins / chemistry*
Saccharomyces cerevisiae Proteins / genetics
Saccharomyces cerevisiae Proteins / metabolism
Substrate Specificity

Substances

Histones
Nucleosomes
Recombinant Proteins
Saccharomyces cerevisiae Proteins
Epl1 protein, S cerevisiae
Esa1 protein, S cerevisiae
Histone Acetyltransferases
NuA4 protein, S cerevisiae
Lysine