8H3H

Human ATAD2 Walker B mutant, ATP state

8H3H の概要

• エントリーDOI: 10.2210/pdb8h3h/pdb
• EMDBエントリー: 34468
• 分子名称: ATPase family AAA domain-containing protein 2, ADENOSINE-5'-DIPHOSPHATE, ADENOSINE-5'-TRIPHOSPHATE (3 entities in total)
• 機能のキーワード: histone chaperone, aaa+ atpase, gene regulation
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 565105.54

構造登録者

Cho, C.,Song, J. (登録日: 2022-10-08, 公開日: 2023-10-18)

主引用文献

Cho, C.,Ganser, C.,Uchihashi, T.,Kato, K.,Song, J.J.
Structure of the human ATAD2 AAA+ histone chaperone reveals mechanism of regulation and inter-subunit communication.
Commun Biol, 6:993-993, 2023

PubMed Abstract: ATAD2 is a non-canonical ATP-dependent histone chaperone and a major cancer target. Despite widespread efforts to design drugs targeting the ATAD2 bromodomain, little is known about the overall structural organization and regulation of ATAD2. Here, we present the 3.1 Å cryo-EM structure of human ATAD2 in the ATP state, showing a shallow hexameric spiral that binds a peptide substrate at the central pore. The spiral conformation is locked by an N-terminal linker domain (LD) that wedges between the seam subunits, thus limiting ATP-dependent symmetry breaking of the AAA+ ring. In contrast, structures of the ATAD2-histone H3/H4 complex show the LD undocked from the seam, suggesting that H3/H4 binding unlocks the AAA+ spiral by allosterically releasing the LD. These findings, together with the discovery of an inter-subunit signaling mechanism, reveal a unique regulatory mechanism for ATAD2 and lay the foundation for developing new ATAD2 inhibitors.

PubMed: 37770645
DOI: 10.1038/s42003-023-05373-1

実験手法

ELECTRON MICROSCOPY (3.15 Å)