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Structure. 2016 Sep 6;24(9):1606-12. doi: 10.1016/j.str.2016.05.023. Epub 2016 Aug 18.

Structural Insights into Histone Crotonyl-Lysine Recognition by the AF9 YEATS Domain.

Author information

1
The First Hospital and Institute of Epigenetic Medicine, Jilin University, Changchun 130061, China; Department of Structural and Chemical Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: qiang.zhang@mssm.edu.
2
The First Hospital and Institute of Epigenetic Medicine, Jilin University, Changchun 130061, China; Department of Structural and Chemical Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
3
The First Hospital and Institute of Epigenetic Medicine, Jilin University, Changchun 130061, China.
4
Department of Structural and Chemical Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
5
Department of Structural and Chemical Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: ming-ming.zhou@mssm.edu.

Abstract

Histone lysine acylations play an important role in the regulation of gene transcription in chromatin. Unlike histone acetyl-lysine, molecular recognition of a recently identified crotonyl-lysine mark is much less understood. Here, we report that the YEATS domain of AF9 preferentially binds crotonyl-lysine over acetyl-lysine in histone H3. Nuclear magnetic resonance structural analysis reveals that crotonyl-lysine of histone H3 lysine 18 is engulfed deep in an aromatic cage of the YEATS domain where the carbonyl oxygen of crotonyl-lysine forms a hydrogen bond with the backbone amide of protein residue Tyr78. The crotonyl-lysine, through its unique electron-rich double-bond side chain, engages π-π aromatic stacking and extended hydrophobic/aromatic interactions with the YEATS domain compared with acetyl-lysine. Our mutational analysis confirmed key protein residues Phe59 and Tyr78 for crotonyl-lysine recognition. Importantly, our findings present a new structural mechanism of protein-protein interactions mediated by histone lysine crotonylation, and show how the cells interpret acyl-lysine marks in different biological contexts.

PMID:
27545619
PMCID:
PMC5014688
DOI:
10.1016/j.str.2016.05.023
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

STATEMENT The authors declare no competing financial interests.

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