4N4F

Crystal Structure of the Bromodomain-PHD Finger Module of Human Transcriptional Co-Activator CBP in complex with di-Acetylated Histone 4 Peptide (H412acK16ac).

Summary for 4N4F

• Entry DOI: 10.2210/pdb4n4f/pdb
• Related: 4N3W
• Descriptor: CREB-binding protein, Histone 4 Peptide, ZINC ION, ... (4 entities in total)
• Functional Keywords: transcriptional co-activator, histone, transcription-protein binding complex, transcription/protein binding
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm: Q92793
• Total number of polymer chains: 2
• Total formula weight: 30405.50

Authors

Plotnikov, A.N.,Zhou, J.,Zhou, M.-M. (deposition date: 2013-10-08, release date: 2014-02-19, Last modification date: 2024-11-06)

Primary citation

Plotnikov, A.N.,Yang, S.,Zhou, T.J.,Rusinova, E.,Frasca, A.,Zhou, M.M.
Structural Insights into Acetylated-Histone H4 Recognition by the Bromodomain-PHD Finger Module of Human Transcriptional Coactivator CBP.
Structure, 22:353-360, 2014

PubMed Abstract: Bromodomain functions as the acetyl-lysine binding domains to regulate gene transcription in chromatin. Bromodomains are rapidly emerging as new epigenetic drug targets for human diseases. However, owing to their transient nature and modest affinity, histone-binding selectivity of bromodomains has remained mostly elusive. Here, we report high-resolution crystal structures of the bromodomain-PHD tandem module of human transcriptional coactivator CBP bound to lysine-acetylated histone H4 peptides. The structures reveal that the PHD finger serves a structural role in the tandem module and that the bromodomain prefers lysine-acetylated motifs comprising a hydrophobic or aromatic residue at -2 and a lysine or arginine at -3 or -4 position from the acetylated lysine. Our study further provides structural insights into distinct modes of singly and diacetylated histone H4 recognition by the bromodomains of CBP and BRD4 that function differently as a transcriptional coactivator and chromatin organizer, respectively, explaining their distinct roles in control of gene expression in chromatin.

PubMed: 24361270
DOI: 10.1016/j.str.2013.10.021

Experimental method

X-RAY DIFFRACTION (1.83 Å)