7K19

CryoEM structure of DNA-PK catalytic subunit complexed with DNA (Complex I)

7K19 の概要

• エントリーDOI: 10.2210/pdb7k19/pdb
• 関連するPDBエントリー: 7K0Y
• EMDBエントリー: 22618 22622
• 分子名称: DNA-dependent protein kinase catalytic subunit, DNA (5'-D(*GP*CP*AP*TP*GP*CP*TP*CP*TP*AP*CP*TP*GP*CP*TP*TP*CP*GP*AP*TP*AP*TP*CP*G)-3'), DNA (5'-D(*AP*AP*GP*CP*AP*GP*TP*AP*GP*AP*GP*CP*AP*TP*GP*C)-3') (3 entities in total)
• 機能のキーワード: nhej, v(d)j recombination, dna repair, dna binding protein, dna binding protein-dna complex, dna binding protein/dna
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 489252.89

構造登録者

Chen, X.,Gellert, M.,Yang, W. (登録日: 2020-09-07, 公開日: 2021-01-06, 最終更新日: 2024-03-06)

主引用文献

Chen, X.,Xu, X.,Chen, Y.,Cheung, J.C.,Wang, H.,Jiang, J.,de Val, N.,Fox, T.,Gellert, M.,Yang, W.
Structure of an activated DNA-PK and its implications for NHEJ.
Mol.Cell, 81:801-810.e3, 2021

PubMed Abstract: DNA-dependent protein kinase (DNA-PK), like all phosphatidylinositol 3-kinase-related kinases (PIKKs), is composed of conserved FAT and kinase domains (FATKINs) along with solenoid structures made of HEAT repeats. These kinases are activated in response to cellular stress signals, but the mechanisms governing activation and regulation remain unresolved. For DNA-PK, all existing structures represent inactive states with resolution limited to 4.3 Å at best. Here, we report the cryoelectron microscopy (cryo-EM) structures of DNA-PKcs (DNA-PK catalytic subunit) bound to a DNA end or complexed with Ku70/80 and DNA in both inactive and activated forms at resolutions of 3.7 Å overall and 3.2 Å for FATKINs. These structures reveal the sequential transition of DNA-PK from inactive to activated forms. Most notably, activation of the kinase involves previously unknown stretching and twisting within individual solenoid segments and loosens DNA-end binding. This unprecedented structural plasticity of helical repeats may be a general regulatory mechanism of HEAT-repeat proteins.

PubMed: 33385326
DOI: 10.1016/j.molcel.2020.12.015

実験手法

ELECTRON MICROSCOPY (4.3 Å)