2QM4

Crystal structure of human XLF/Cernunnos, a non-homologous end-joining factor

2QM4 の概要

• エントリーDOI: 10.2210/pdb2qm4/pdb
• 関連するPDBエントリー: 1fu1 1ik9
• 分子名称: Non-homologous end-joining factor 1 (2 entities in total)
• 機能のキーワード: xrcc4 like factor, homodimer, beta-sandwich, coiled-coil, recombination
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus : Q9H9Q4
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 108239.16

構造登録者

Li, Y.,Chirgadze, D.Y.,Sibanda, B.L.,Bolanos-Garcia, V.M.,Davies, O.R.,Blundell, T.L. (登録日: 2007-07-14, 公開日: 2007-12-11, 最終更新日: 2024-10-30)

主引用文献

Li, Y.,Chirgadze, D.Y.,Bolanos-Garcia, V.M.,Sibanda, B.L.,Davies, O.R.,Ahnesorg, P.,Jackson, S.P.,Blundell, T.L.
Crystal structure of human XLF/Cernunnos reveals unexpected differences from XRCC4 with implications for NHEJ.
Embo J., 27:290-300, 2008

PubMed Abstract: The recently characterised 299-residue human XLF/Cernunnos protein plays a crucial role in DNA repair by non-homologous end joining (NHEJ) and interacts with the XRCC4-DNA Ligase IV complex. Here, we report the crystal structure of the XLF (1-233) homodimer at 2.3 A resolution, confirming the predicted structural similarity to XRCC4. The XLF coiled-coil, however, is shorter than that of XRCC4 and undergoes an unexpected reverse in direction giving rise to a short distorted four helical bundle and a C-terminal helical structure wedged between the coiled-coil and head domain. The existence of a dimer as the major species is confirmed by size-exclusion chromatography, analytical ultracentrifugation, small-angle X-ray scattering and other biophysical methods. We show that the XLF structure is not easily compatible with a proposed XRCC4:XLF heterodimer. However, we demonstrate interactions between dimers of XLF and XRCC4 by surface plasmon resonance and analyse these in terms of surface properties, amino-acid conservation and mutations in immunodeficient patients. Our data are most consistent with head-to-head interactions in a 2:2:1 XRCC4:XLF:Ligase IV complex.

PubMed: 18046455
DOI: 10.1038/sj.emboj.7601942

実験手法

X-RAY DIFFRACTION (2.3 Å)