7ZYG

CryoEM structure of Ku heterodimer bound to DNA, PAXX and XLF

7ZYG の概要

• エントリーDOI: 10.2210/pdb7zyg/pdb
• EMDBエントリー: 15022
• 分子名称: X-ray repair cross-complementing protein 6, X-ray repair cross-complementing protein 5, Protein PAXX, ... (7 entities in total)
• 機能のキーワード: nhej, ku70, ku80, dna damage, dna binding protein, xlf
• 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: 217065.19

構造登録者

Hardwick, S.W.,Kefala-Stavridi, A.,Chirgadze, D.Y.,Blundell, T.L.,Chaplin, A.K. (登録日: 2022-05-24, 公開日: 2023-06-07, 最終更新日: 2024-07-24)

主引用文献

Seif-El-Dahan, M.,Kefala-Stavridi, A.,Frit, P.,Hardwick, S.W.,Chirgadze, D.Y.,Maia De Oliviera, T.,Britton, S.,Barboule, N.,Bossaert, M.,Pandurangan, A.P.,Meek, K.,Blundell, T.L.,Ropars, V.,Calsou, P.,Charbonnier, J.B.,Chaplin, A.K.
PAXX binding to the NHEJ machinery explains functional redundancy with XLF.
Sci Adv, 9:eadg2834-eadg2834, 2023

PubMed Abstract: Nonhomologous end joining is a critical mechanism that repairs DNA double-strand breaks in human cells. In this work, we address the structural and functional role of the accessory protein PAXX [paralog of x-ray repair cross-complementing protein 4 (XRCC4) and XRCC4-like factor (XLF)] in this mechanism. Here, we report high-resolution cryo-electron microscopy (cryo-EM) and x-ray crystallography structures of the PAXX C-terminal Ku-binding motif bound to Ku70/80 and cryo-EM structures of PAXX bound to two alternate DNA-dependent protein kinase (DNA-PK) end-bridging dimers, mediated by either Ku80 or XLF. We identify residues critical for the Ku70/PAXX interaction in vitro and in cells. We demonstrate that PAXX and XLF can bind simultaneously to the Ku heterodimer and act as structural bridges in alternate forms of DNA-PK dimers. Last, we show that engagement of both proteins provides a complementary advantage for DNA end synapsis and end joining in cells.

PubMed: 37256950
DOI: 10.1126/sciadv.adg2834

実験手法

ELECTRON MICROSCOPY (2.68 Å)