2. Academic Validation
  3. Structural Insights into Histone Crotonyl-Lysine Recognition by the AF9 YEATS Domain

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

  • Structure. 2016 Sep 6;24(9):1606-12. doi: 10.1016/j.str.2016.05.023.
Qiang Zhang 1,  Lei Zeng 2,  Chengcheng Zhao 3,  Ying Ju 3,  Tsuyoshi Konuma 4,  Ming-Ming Zhou 5
Affiliations

Affiliations

  • 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.
PMID: 27545619 DOI: 10.1016/j.str.2016.05.023
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.

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