4QUU

Structure of the bromodomain of human ATPase family AAA domain-containing protein 2 (ATAD2) complexed with Histone H4-K(ac)5

Summary for 4QUU

• Entry DOI: 10.2210/pdb4quu/pdb
• Related: 4QUT
• Descriptor: ATPase family AAA domain-containing protein 2, Histone H4, SULFATE ION, ... (5 entities in total)
• Functional Keywords: structural genomics, structural genomics consortium, sgc, signaling protein, bromodomain, actyl-lysine binding, atpase family aaa domain-containing protein 2, epigenetics, histone, bromodomain-histone, structural genomics consortium (sgc)
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus : Q6PL18 P62805
• Total number of polymer chains: 2
• Total formula weight: 17540.80

Authors

Chaikuad, A.,Felletar, I.,von Delft, F.,Arrowsmith, C.H.,Edwards, A.M.,Bountra, C.,Knapp, S.,Structural Genomics Consortium (SGC) (deposition date: 2014-07-12, release date: 2014-07-30, Last modification date: 2023-12-06)

Primary citation

Morozumi, Y.,Boussouar, F.,Tan, M.,Chaikuad, A.,Jamshidikia, M.,Colak, G.,He, H.,Nie, L.,Petosa, C.,de Dieuleveult, M.,Curtet, S.,Vitte, A.L.,Rabatel, C.,Debernardi, A.,Cosset, F.L.,Verhoeyen, E.,Emadali, A.,Schweifer, N.,Gianni, D.,Gut, M.,Guardiola, P.,Rousseaux, S.,Gerard, M.,Knapp, S.,Zhao, Y.,Khochbin, S.
Atad2 is a generalist facilitator of chromatin dynamics in embryonic stem cells.
J Mol Cell Biol, 8:349-362, 2016

PubMed Abstract: Although the conserved AAA ATPase and bromodomain factor, ATAD2, has been described as a transcriptional co-activator upregulated in many cancers, its function remains poorly understood. Here, using a combination of ChIP-seq, ChIP-proteomics, and RNA-seq experiments in embryonic stem cells where Atad2 is normally highly expressed, we found that Atad2 is an abundant nucleosome-bound protein present on active genes, associated with chromatin remodelling, DNA replication, and DNA repair factors. A structural analysis of its bromodomain and subsequent investigations demonstrate that histone acetylation guides ATAD2 to chromatin, resulting in an overall increase of chromatin accessibility and histone dynamics, which is required for the proper activity of the highly expressed gene fraction of the genome. While in exponentially growing cells Atad2 appears dispensable for cell growth, in differentiating ES cells Atad2 becomes critical in sustaining specific gene expression programmes, controlling proliferation and differentiation. Altogether, this work defines Atad2 as a facilitator of general chromatin-templated activities such as transcription.

PubMed: 26459632
DOI: 10.1093/jmcb/mjv060

Experimental method

X-RAY DIFFRACTION (1.8 Å)