Summary for 8BHV
| Entry DOI | 10.2210/pdb8bhv/pdb |
| EMDB information | 16070 |
| Descriptor | DNA-dependent protein kinase catalytic subunit, DNA (28-MER), DNA (24-MER), ... (11 entities in total) |
| Functional Keywords | dna-pk, dna-pkcs, ku70, ku80, paxx, nhej, dna binding protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 20 |
| Total formula weight | 1748235.24 |
| Authors | Hardwick, S.W.,Chaplin, A.K. (deposition date: 2022-11-01, release date: 2023-06-07, Last modification date: 2024-07-24) |
| 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 Cited by 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: 37256950DOI: 10.1126/sciadv.adg2834 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (4.51 Å) |
Structure validation
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