EMD-25439

Single-particle
3.3 Å
EMD-25439 Deposition: 16/11/2021
Map released: 12/01/2022
Last modified: 05/06/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-25439

CryoEM structure of DNA-PK complex VII

EMD-25439

Single-particle
3.3 Å
EMD-25439 Deposition: 16/11/2021
Map released: 12/01/2022
Last modified: 05/06/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Homo sapiens, Escherichia coli
Sample: DNA-PK Complex VII
Fitted models: 7su3 (Avg. Q-score: 0.528)

Deposition Authors: Chen X , Liu L
Autophosphorylation transforms DNA-PK from protecting to processing DNA ends.
Liu L, Chen X , Li J, Wang H, Buehl CJ , Goff NJ, Meek K, Yang W , Gellert M
(2022) Mol Cell , 82 , 177
PUBMED: 34936881
DOI: doi:10.1016/j.molcel.2021.11.025
ISSN: 1097-2765
ASTM: MOCEFL
Abstract:
The DNA-dependent protein kinase (DNA-PK) initially protects broken DNA ends but then promotes their processing during non-homologous end joining (NHEJ). Before ligation by NHEJ, DNA hairpin ends generated during V(D)J recombination must be opened by the Artemis nuclease, together with autophosphorylated DNA-PK. Structures of DNA-PK bound to DNA before and after phosphorylation, and in complex with Artemis and a DNA hairpin, reveal an essential functional switch. When bound to open DNA ends in its protection mode, DNA-PK is inhibited for cis-autophosphorylation of the so-called ABCDE cluster but activated for phosphorylation of other targets. In contrast, DNA hairpin ends promote cis-autophosphorylation. Phosphorylation of four Thr residues in ABCDE leads to gross structural rearrangement of DNA-PK, widening the DNA binding groove for Artemis recruitment and hairpin cleavage. Meanwhile, Artemis locks DNA-PK into the kinase-inactive state. Kinase activity and autophosphorylation of DNA-PK are regulated by different DNA ends, feeding forward to coordinate NHEJ events.