8UK5

Crystal structure of the bromodomain of human ATAD2B in complex with histone H4S1(ph)K5ac

8UK5 の概要

• エントリーDOI: 10.2210/pdb8uk5/pdb
• 分子名称: ATPase family AAA domain-containing protein 2B, Histone H4S1(ph)K5ac (3 entities in total)
• 機能のキーワード: bromodomain, epigenetics, chromatin reader domain, protein binding, histone acetylation, peptide binding protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 17166.50

構造登録者

Montgomery, C.,Phillips, M.,Nix, J.C.,Glass, K.C. (登録日: 2023-10-12, 公開日: 2024-06-05, 最終更新日: 2024-11-13)

主引用文献

Phillips, M.,Malone, K.L.,Boyle, B.W.,Montgomery, C.,Kressy, I.A.,Joseph, F.M.,Bright, K.M.,Boyson, S.P.,Chang, S.,Nix, J.C.,Young, N.L.,Jeffers, V.,Frietze, S.,Glass, K.C.
Impact of Combinatorial Histone Modifications on Acetyllysine Recognition by the ATAD2 and ATAD2B Bromodomains.
J.Med.Chem., 67:8186-8200, 2024

PubMed Abstract: The ATPase family AAA domain containing 2 (ATAD2) protein and its paralog ATAD2B have a C-terminal bromodomain (BRD) that functions as a reader of acetylated lysine residues on histone proteins. Using a structure-function approach, we investigated the ability of the ATAD2/B BRDs to select acetylated lysine among multiple histone post-translational modifications. The ATAD2B BRD can bind acetylated histone ligands that also contain adjacent methylation or phosphorylation marks, while the presence of these modifications significantly weakened the acetyllysine binding activity of the ATAD2 BRD. Our structural studies provide mechanistic insights into how ATAD2/B BRD-binding pocket residues coordinate the acetyllysine group in the context of adjacent post-translational modifications. Furthermore, we investigated how sequence changes in amino acids of the histone ligands impact the recognition of an adjacent acetyllysine residue. Our study highlights how the interplay between multiple combinations of histone modifications influences the reader activity of the ATAD2/B BRDs, resulting in distinct binding modes.

PubMed: 38733345
DOI: 10.1021/acs.jmedchem.4c00210

実験手法

X-RAY DIFFRACTION (1.4 Å)