2KWO

Solution structure of the double PHD (plant homeodomain) fingers of human transcriptional protein DPF3b bound to a histone H4 peptide containing N-terminal acetylation at Serine 1

Summary for 2KWO

• Entry DOI: 10.2210/pdb2kwo/pdb
• Related: 2kwj 2kwk 2kwo
• NMR Information: BMRB: 16865
• Descriptor: Histone peptide, Zinc finger protein DPF3, ZINC ION (3 entities in total)
• Functional Keywords: acetyl-lysine, transcription regulation, nucleus, metal binding protein
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus (Probable): Q92784
• Total number of polymer chains: 2
• Total formula weight: 15051.51

Authors

Zeng, L.,Zhang, Q.,Li, S.,Plotnikov, A.N.,Walsh, M.J.,Zhou, M. (deposition date: 2010-04-14, release date: 2010-07-14, Last modification date: 2025-03-26)

Primary citation

Zeng, L.,Zhang, Q.,Li, S.,Plotnikov, A.N.,Walsh, M.J.,Zhou, M.M.
Mechanism and regulation of acetylated histone binding by the tandem PHD finger of DPF3b.
Nature, 466:258-262, 2010

PubMed Abstract: Histone lysine acetylation and methylation have an important role during gene transcription in a chromatin context. Knowledge concerning the types of protein modules that can interact with acetyl-lysine has so far been limited to bromodomains. Recently, a tandem plant homeodomain (PHD) finger (PHD1-PHD2, or PHD12) of human DPF3b, which functions in association with the BAF chromatin remodelling complex to initiate gene transcription during heart and muscle development, was reported to bind histones H3 and H4 in an acetylation-sensitive manner, making it the first alternative to bromodomains for acetyl-lysine binding. Here we report the structural mechanism of acetylated histone binding by the double PHD fingers of DPF3b. Our three-dimensional solution structures and biochemical analysis of DPF3b highlight the molecular basis of the integrated tandem PHD finger, which acts as one functional unit in the sequence-specific recognition of lysine-14-acetylated histone H3 (H3K14ac). Whereas the interaction with H3 is promoted by acetylation at lysine 14, it is inhibited by methylation at lysine 4, and these opposing influences are important during transcriptional activation of the mouse DPF3b target genes Pitx2 and Jmjd1c. Binding of this tandem protein module to chromatin can thus be regulated by different histone modifications during the initiation of gene transcription.

PubMed: 20613843
DOI: 10.1038/nature09139

Experimental method

SOLUTION NMR