4OUF

Crystal Structure of CBP bromodomain

Summary for 4OUF

• Entry DOI: 10.2210/pdb4ouf/pdb
• Descriptor: CREB-binding protein, DI(HYDROXYETHYL)ETHER, 1,2-ETHANEDIOL, ... (4 entities in total)
• Functional Keywords: transferase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: Q92793
• Total number of polymer chains: 2
• Total formula weight: 28050.16

Authors

Roy, S.,Das, C.,Tyler, J.K.,Kutateladze, T.G. (deposition date: 2014-02-17, release date: 2014-03-12, Last modification date: 2023-09-20)

Primary citation

Das, C.,Roy, S.,Namjoshi, S.,Malarkey, C.S.,Jones, D.N.,Kutateladze, T.G.,Churchill, M.E.,Tyler, J.K.
Binding of the histone chaperone ASF1 to the CBP bromodomain promotes histone acetylation.
Proc.Natl.Acad.Sci.USA, 111:E1072-E1081, 2014

PubMed Abstract: The multifunctional Creb-binding protein (CBP) protein plays a pivotal role in many critical cellular processes. Here we demonstrate that the bromodomain of CBP binds to histone H3 acetylated on lysine 56 (K56Ac) with higher affinity than to its other monoacetylated binding partners. We show that autoacetylation of CBP is critical for the bromodomain-H3 K56Ac interaction, and we propose that this interaction occurs via autoacetylation-induced conformation changes in CBP. Unexpectedly, the bromodomain promotes acetylation of H3 K56 on free histones. The CBP bromodomain also interacts with the histone chaperone anti-silencing function 1 (ASF1) via a nearby but distinct interface. This interaction is necessary for ASF1 to promote acetylation of H3 K56 by CBP, indicating that the ASF1-bromodomain interaction physically delivers the histones to the histone acetyl transferase domain of CBP. A CBP bromodomain mutation manifested in Rubinstein-Taybi syndrome has compromised binding to both H3 K56Ac and ASF1, suggesting that these interactions are important for the normal function of CBP.

PubMed: 24616510
DOI: 10.1073/pnas.1319122111

Experimental method

X-RAY DIFFRACTION (1.4 Å)