7Z88

DNA-PK in the intermediate state

7Z88 の概要

• エントリーDOI: 10.2210/pdb7z88/pdb
• EMDBエントリー: 14546
• 分子名称: DNA-dependent protein kinase catalytic subunit, X-ray repair cross-complementing protein 6, X-ray repair cross-complementing protein 5, ... (6 entities in total)
• 機能のキーワード: dna-dependent protein kinase, dna binding protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 638890.89

構造登録者

Liang, S.,Blundell, T.L. (登録日: 2022-03-16, 公開日: 2023-01-18, 最終更新日: 2024-07-24)

主引用文献

Liang, S.,Blundell, T.L.
Human DNA-dependent protein kinase activation mechanism.
Nat.Struct.Mol.Biol., 30:140-147, 2023

PubMed Abstract: DNA-dependent protein kinase (DNA-PK), a multicomponent complex including the DNA-PK catalytic subunit and Ku70/80 heterodimer together with DNA, is central to human DNA damage response and repair. Using a DNA-PK-selective inhibitor (M3814), we identified from one dataset two cryo-EM structures of the human DNA-PK complex in different states, the intermediate state and the active state. Here we show that activation of the kinase is regulated through conformational changes caused by the binding ligand and the string region (residues 802-846) of the DNA-PK catalytic subunit, particularly the helix-hairpin-helix motif (residues 816-836) that interacts with DNA. These observations demonstrate the regulatory role of the ligand and explain why DNA-PK is DNA dependent. Cooperation and coordination among binding partners, disordered flexible regions and mechanically flexible HEAT repeats modulate the activation of the kinase. Together with previous findings, these results provide a better molecular understanding of DNA-PK catalysis.

PubMed: 36604499
DOI: 10.1038/s41594-022-00881-w

実験手法

ELECTRON MICROSCOPY (3.33 Å)