5GH9

Crystal structure of CBP Bromodomain with H3K56ac peptide

5GH9 の概要

• エントリーDOI: 10.2210/pdb5gh9/pdb
• 分子名称: CREB-binding protein, Histone H3 (3 entities in total)
• 機能のキーワード: h3k56ac bromodomain, transcription
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Cytoplasm: Q92793; Chromosome . Nucleus : K7EMV3
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 15939.34

構造登録者

Xu, L. (登録日: 2016-06-19, 公開日: 2017-06-21, 最終更新日: 2023-11-15)

主引用文献

Xu, L.,Cheng, A.,Huang, M.,Zhang, J.,Jiang, Y.,Wang, C.,Li, F.,Bao, H.,Gao, J.,Wang, N.,Liu, J.,Wu, J.,Wong, C.C.L.,Ruan, K.
Structural insight into CBP bromodomain-mediated recognition of acetylated histone H3K56ac
FEBS J., 2017

PubMed Abstract: 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 αN 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 α region within an H3-H4 dimer, which is expected to facilitate the HAT activity of CBP for subsequent H3K56 acetylation of free histones.

PubMed: 28815970
DOI: 10.1111/febs.14198

実験手法

X-RAY DIFFRACTION (1.451 Å)