The NuA4 Core Complex Acetylates Nucleosomal Histone H4 through a Double Recognition Mechanism.
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.
MOE Key Laboratory of Protein Science, Tsinghua University, Beijing 100086, China; School of Life Science, Tsinghua University, Beijing 100086, China.
Peng
P
Xu
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.
Chengmin
C
Li
MOE Key Laboratory of Protein Science, Tsinghua University, Beijing 100086, China; School of Life Science, Tsinghua University, Beijing 100086, China.
Zhihong
Z
Chen
School of Life Science, Tsinghua University, Beijing 100086, China.
Shuanying
S
Jiang
School of Life Science, Tsinghua University, Beijing 100086, China.
Shilong
S
Fan
State Key Laboratory of Bio-membrane and Membrane Biotechnology, Tsinghua University, Beijing 100086, China.
Jiawei
J
Wang
School of Life Science, Tsinghua University, Beijing 100086, China.
Junbiao
J
Dai
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: zhup@ibp.ac.cn.
Ping
P
Zhu
MOE Key Laboratory of Protein Science, Tsinghua University, Beijing 100086, China; School of Life Science, Tsinghua University, Beijing 100086, China. Electronic address: zhucheng_chen@tsinghua.edu.cn.
Zhucheng
Z
Chen
D000107:Acetylation; D000595:Amino Acid Sequence; D020134:Catalytic Domain; D003001:Cloning, Molecular; D020285:Cryoelectron Microscopy; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D051548:Histone Acetyltransferases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008239:Lysine / Q000737:chemistry / Q000378:metabolism; D062105:Molecular Docking Simulation; D009707:Nucleosomes / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D011499:Protein Processing, Post-Translational; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity
D006657:Histones; D009707:Nucleosomes; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; C580641:Epl1 protein, S cerevisiae; C496551:Esa1 protein, S cerevisiae; D051548:Histone Acetyltransferases; C504740:NuA4 protein, S cerevisiae; D008239:Lysine