6BKG

Human LigIV catalytic domain with bound DNA-adenylate intermediate in closed conformation

6BKG の概要

• エントリーDOI: 10.2210/pdb6bkg/pdb
• 分子名称: DNA ligase 4, DNA (5'-D(*GP*CP*TP*GP*AP*TP*GP*CP*GP*TP*C)-3'), DNA (5'-D(*GP*TP*CP*CP*GP*AP*CP*GP*AP*CP*GP*CP*AP*TP*CP*AP*GP*C)-3'), ... (9 entities in total)
• 機能のキーワード: dna double-strand break repair, ligase, nonhomologous end-joining, ligase-dna complex, ligase/dna
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 82189.00

構造登録者

Moon, A.F.,Tumbale, P.P.,Schellenberg, M.J.,Williams, R.S.,Williams, J.G.,Kunkel, T.A.,Pedersen, L.C.,Bebenek, B. (登録日: 2017-11-08, 公開日: 2018-07-18, 最終更新日: 2023-10-04)

主引用文献

Kaminski, A.M.,Tumbale, P.P.,Schellenberg, M.J.,Williams, R.S.,Williams, J.G.,Kunkel, T.A.,Pedersen, L.C.,Bebenek, K.
Structures of DNA-bound human ligase IV catalytic core reveal insights into substrate binding and catalysis.
Nat Commun, 9:2642-2642, 2018

PubMed Abstract: DNA ligase IV (LigIV) performs the final DNA nick-sealing step of classical nonhomologous end-joining, which is critical for immunoglobulin gene maturation and efficient repair of genotoxic DNA double-strand breaks. Hypomorphic LigIV mutations cause extreme radiation sensitivity and immunodeficiency in humans. To better understand the unique features of LigIV function, here we report the crystal structure of the catalytic core of human LigIV in complex with a nicked nucleic acid substrate in two distinct states-an open lysyl-AMP intermediate, and a closed DNA-adenylate form. Results from structural and mutagenesis experiments unveil a dynamic LigIV DNA encirclement mechanism characterized by extensive interdomain interactions and active site phosphoanhydride coordination, all of which are required for efficient DNA nick sealing. These studies provide a scaffold for defining impacts of LigIV catalytic core mutations and deficiencies in human LIG4 syndrome.

PubMed: 29980672
DOI: 10.1038/s41467-018-05024-8

実験手法

X-RAY DIFFRACTION (2.402 Å)