7K11

CryoEM structure of inactivated-form FATKIN domain of DNA-PK

Summary for 7K11

• Entry DOI: 10.2210/pdb7k11/pdb
• Related: 7K0Y
• EMDB information: 22618 22620
• Descriptor: DNA-dependent protein kinase catalytic subunit (1 entity in total)
• Functional Keywords: nhej, pikk kinase, v(d)j recombination, dna binding protein, dna binding protein-dna complex, dna binding protein/dna
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 469673.22

Authors

Chen, X.,Gellert, M.,Yang, W. (deposition date: 2020-09-06, release date: 2021-01-06, Last modification date: 2024-03-06)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (3.21 Å)