8ASC

Ku70/80 binds to the Ku-binding motif of PAXX

Summary for 8ASC

• Entry DOI: 10.2210/pdb8asc/pdb
• Descriptor: X-ray repair cross-complementing protein 6, X-ray repair cross-complementing protein 5, DNA (5'-D(P*CP*GP*GP*AP*TP*CP*GP*AP*GP*GP*GP*CP*CP*CP*GP*AP*TP*AP*T)-3'), ... (7 entities in total)
• Functional Keywords: nhej, dna repair, dna binding protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 18
• Total formula weight: 573910.75

Authors

Seif El Dahan, M.,Ropars, V.,Charbonnier, J.B. (deposition date: 2022-08-19, release date: 2023-06-21, Last modification date: 2024-10-16)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.95 Å)