6ERF

Complex of APLF factor and Ku heterodimer bound to DNA

Summary for 6ERF

• Entry DOI: 10.2210/pdb6erf/pdb
• Descriptor: X-ray repair cross-complementing protein 6, X-ray repair cross-complementing protein 5, DNA (5'-D(*GP*TP*TP*TP*TP*TP*AP*GP*TP*TP*TP*AP*TP*TP*GP*GP*GP*CP*GP*CP*G)-3'), ... (6 entities in total)
• Functional Keywords: dna repair protein nhej, dna binding protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 20
• Total formula weight: 588176.31

Authors

Nemoz, C.,Legrand, P.,Ropars, V.,Charbonnier, J.B. (deposition date: 2017-10-18, release date: 2018-10-17, Last modification date: 2024-01-17)

Primary citation

Nemoz, C.,Ropars, V.,Frit, P.,Gontier, A.,Drevet, P.,Yu, J.,Guerois, R.,Pitois, A.,Comte, A.,Delteil, C.,Barboule, N.,Legrand, P.,Baconnais, S.,Yin, Y.,Tadi, S.,Barbet-Massin, E.,Berger, I.,Le Cam, E.,Modesti, M.,Rothenberg, E.,Calsou, P.,Charbonnier, J.B.
XLF and APLF bind Ku80 at two remote sites to ensure DNA repair by non-homologous end joining.
Nat.Struct.Mol.Biol., 25:971-980, 2018

PubMed Abstract: The Ku70-Ku80 (Ku) heterodimer binds rapidly and tightly to the ends of DNA double-strand breaks and recruits factors of the non-homologous end-joining (NHEJ) repair pathway through molecular interactions that remain unclear. We have determined crystal structures of the Ku-binding motifs (KBM) of the NHEJ proteins APLF (A-KBM) and XLF (X-KBM) bound to a Ku-DNA complex. The two KBM motifs bind remote sites of the Ku80 α/β domain. The X-KBM occupies an internal pocket formed by an unprecedented large outward rotation of the Ku80 α/β domain. We observe independent recruitment of the APLF-interacting protein XRCC4 and of XLF to laser-irradiated sites via binding of A- and X-KBMs, respectively, to Ku80. Finally, we show that mutation of the X-KBM and A-KBM binding sites in Ku80 compromises both the efficiency and accuracy of end joining and cellular radiosensitivity. A- and X-KBMs may represent two initial anchor points to build the intricate interaction network required for NHEJ.

PubMed: 30291363
DOI: 10.1038/s41594-018-0133-6

Experimental method

X-RAY DIFFRACTION (3.01 Å)