7SGL

DNA-PK complex of DNA end processing

7SGL の概要

• エントリーDOI: 10.2210/pdb7sgl/pdb
• EMDBエントリー: 25113
• 分子名称: DNA-dependent protein kinase catalytic subunit, X-ray repair cross-complementing protein 6, X-ray repair cross-complementing protein 5, ... (9 entities in total)
• 機能のキーワード: endonuclease, kinase, complex, dna binding protein, transferase, 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: 6
• 化学式量合計: 737062.08

構造登録者

Liu, L.,Li, J.,Chen, X.,Yang, W.,Gellert, M. (登録日: 2021-10-06, 公開日: 2022-01-12, 最終更新日: 2024-10-23)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (3 Å)