3SR2

Crystal Structure of Human XLF-XRCC4 Complex

3SR2 の概要

• エントリーDOI: 10.2210/pdb3sr2/pdb
• 分子名称: DNA repair protein XRCC4, Non-homologous end-joining factor 1 (2 entities in total)
• 機能のキーワード: xrcc4, xlf, nhej, dna repair, dna, dna ligases, dna-binding proteins, dimerization, humans, protein structure, quaternary, complex, non-homologous end joining (nhej), dna ligase iv, ku, xlf-xrcc4, protein dna-interaction, dna binding protein-protein binding complex, dna binding protein/protein binding
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Nucleus: Q13426 Q9H9Q4
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 168501.06

構造登録者

Hammel, M.,Classen, S.,Tainer, J.A. (登録日: 2011-07-06, 公開日: 2011-07-20, 最終更新日: 2023-09-13)

主引用文献

Hammel, M.,Rey, M.,Yu, Y.,Mani, R.S.,Classen, S.,Liu, M.,Pique, M.E.,Fang, S.,Mahaney, B.L.,Weinfeld, M.,Schriemer, D.C.,Lees-Miller, S.P.,Tainer, J.A.
XRCC4 Protein Interactions with XRCC4-like Factor (XLF) Create an Extended Grooved Scaffold for DNA Ligation and Double Strand Break Repair.
J.Biol.Chem., 286:32638-32650, 2011

PubMed Abstract: The XRCC4-like factor (XLF)-XRCC4 complex is essential for nonhomologous end joining, the major repair pathway for DNA double strand breaks in human cells. Yet, how XLF binds XRCC4 and impacts nonhomologous end joining functions has been enigmatic. Here, we report the XLF-XRCC4 complex crystal structure in combination with biophysical and mutational analyses to define the XLF-XRCC4 interactions. Crystal and solution structures plus mutations characterize alternating XRCC4 and XLF head domain interfaces forming parallel super-helical filaments. XLF Leu-115 ("Leu-lock") inserts into a hydrophobic pocket formed by XRCC4 Met-59, Met-61, Lys-65, Lys-99, Phe-106, and Leu-108 in synergy with pseudo-symmetric β-zipper hydrogen bonds to drive specificity. XLF C terminus and DNA enhance parallel filament formation. Super-helical XLF-XRCC4 filaments form a positively charged channel to bind DNA and align ends for efficient ligation. Collective results reveal how human XLF and XRCC4 interact to bind DNA, suggest consequences of patient mutations, and support a unified molecular mechanism for XLF-XRCC4 stimulation of DNA ligation.

PubMed: 21775435
DOI: 10.1074/jbc.M111.272641

実験手法

X-RAY DIFFRACTION (3.9708 Å)