7SU3

CryoEM structure of DNA-PK complex VII

Summary for 7SU3

• Entry DOI: 10.2210/pdb7su3/pdb
• EMDB information: 25110 25111 25112 25439
• Descriptor: DNA-dependent protein kinase catalytic subunit, X-ray repair cross-complementing protein 6, X-ray repair cross-complementing protein 5, ... (7 entities in total)
• Functional Keywords: nhej, dna-pk, kinase, dna repair, dna binding protein, dna binding protein-dna complex, dna binding protein/dna
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 7
• Total formula weight: 648133.83

Authors

Chen, X.,Liu, L.,Gellert, M.,Yang, W. (deposition date: 2021-11-16, release date: 2022-01-12, Last modification date: 2025-05-14)

Primary citation

Liu, L.,Chen, X.,Li, J.,Wang, H.,Buehl, C.J.,Goff, N.J.,Meek, K.,Yang, W.,Gellert, M.
Autophosphorylation transforms DNA-PK from protecting to processing DNA ends.
Mol.Cell, 82:177-, 2022

PubMed 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.

PubMed: 34936881
DOI: 10.1016/j.molcel.2021.11.025

Experimental method

ELECTRON MICROSCOPY (3.3 Å)