3II6

Structure of human Xrcc4 in complex with the tandem BRCT domains of DNA LigaseIV.

3II6 の概要

• エントリーDOI: 10.2210/pdb3ii6/pdb
• 分子名称: DNA repair protein XRCC4, DNA ligase 4, CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: xrcc4, dna ligase iv, nhej, dna repair, brct, alternative splicing, coiled coil, dna damage, dna recombination, isopeptide bond, nucleus, phosphoprotein, polymorphism, ubl conjugation, atp-binding, cell cycle, cell division, disease mutation, dna replication, ligase, magnesium, metal-binding, nucleotide-binding, scid, ligase-dna binding protein complex, ligase/dna binding protein
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Nucleus: Q13426 P49917
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 154211.77

構造登録者

Meesala, S.,Junop, M. (登録日: 2009-07-31, 公開日: 2009-08-11, 最終更新日: 2024-02-21)

主引用文献

Wu, P.Y.,Frit, P.,Meesala, S.,Dauvillier, S.,Modesti, M.,Andres, S.N.,Huang, Y.,Sekiguchi, J.,Calsou, P.,Salles, B.,Junop, M.S.
Structural and functional interaction between the human DNA repair proteins DNA ligase IV and XRCC4
MOL.CELL.BIOL., 11:3163-3172, 2009

PubMed Abstract: Nonhomologous end-joining represents the major pathway used by human cells to repair DNA double-strand breaks. It relies on the XRCC4/DNA ligase IV complex to reseal DNA strands. Here we report the high-resolution crystal structure of human XRCC4 bound to the carboxy-terminal tandem BRCT repeat of DNA ligase IV. The structure differs from the homologous Saccharomyces cerevisiae complex and reveals an extensive DNA ligase IV binding interface formed by a helix-loop-helix structure within the inter-BRCT linker region, as well as significant interactions involving the second BRCT domain, which induces a kink in the tail region of XRCC4. We further demonstrate that interaction with the second BRCT domain of DNA ligase IV is necessary for stable binding to XRCC4 in cells, as well as to achieve efficient dominant-negative effects resulting in radiosensitization after ectopic overexpression of DNA ligase IV fragments in human fibroblasts. Together our findings provide unanticipated insight for understanding the physical and functional architecture of the nonhomologous end-joining ligation complex.

PubMed: 19332554

実験手法

X-RAY DIFFRACTION (2.4 Å)