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Structural insight into the recognition of acetylated histone H3K56ac mediated by the bromodomain of CREB-binding protein

  • [设施]:上海设施
  • [期刊/会议名称]:FEBS Journal
  • [摘要]:The acetylation of lysine 56 of histone H3 (H3K56ac) enhances the binding affinity of histone chaperones to H3-H4 dimers. CREB-binding protein (CBP) possesses a bromodomain that recognizes H3K56 acetylation. CBP also possesses a histone acetyltransferase (HAT) domain, which has been shown to promote H3K56 acetylation of free histones to facilitate delivery of replication-dependent chaperones to acetylated histones for chromatin assembly. However, the mechanism by which the CBP bromodomain recognizes H3K56ac and the context in which such recognition occurs remain elusive. Here, we solved the crystal structure of the CBP bromodomain in complex with an H3K56ac peptide. Our data demonstrate that the CBP bromodomain recognizes H3K56ac with high affinity. Structural and affinity analyses reveal that the CBP bromodomain prefers an aromatic residue at the -2 position and an arginine at the -4 position from the acetyl-lysine, and that the CBP bromodomain selectively recognizes an extended conformation of the H3 alpha N helix that contains H3K56ac. We also demonstrate that the CBP bromodomain binds to H3K56ac in a recombinant H3-H4 dimer but not in a mono-nucleosome. Our results suggest that the CBP bromodomain selectively recognizes an extended conformation of the K56-acetylated H3 alpha(N) region within an H3-H4 dimer, which is expected to facilitate the HAT activity of CBP for subsequent H3K56 acetylation of free histones.
  • [发表日期]:2017
  • [第一作者]:徐莉
  • [第一作者单位]:中国科学技术大学
  • [通讯作者]:阮科
  • [通讯作者单位]:中国科学技术大学
  • [论文类型]:0
  • [期刊分类]:SCI2区
  • [学科分类]:生物学_生物化学
  • [影响因子]:3.902
  • [关键词]:bromodomain; CBP; H3K56 acetylation; histone acetylation; post-translational modifications
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