title: Structure of the catalytic region of DNA ligase IV in complex with an Artemis fragment sheds light on double-strand break repair.
abstract: Nonhomologous end joining (NHEJ) is central to the repair of double-stranded DNA breaks throughout the cell cycle and plays roles in the development of the immune system. Although three-dimensional structures of most components of NHEJ have been defined, those of the catalytic region of DNA ligase IV (LigIV), a specialized DNA ligase known to work in NHEJ, and of Artemis have remained unresolved. Here, we report the crystal structure at 2.4 Å resolution of the catalytic region of LigIV (residues 1-609) in complex with an Artemis peptide. We describe interactions of the DNA-binding domain of LigIV with the continuous epitope of Artemis, which, together, form a three-helix bundle. A kink in the first helix of LigIV introduced by a conserved VPF motif gives rise to a hydrophobic pocket, which accommodates a conserved tryptophan from Artemis. We provide structural insights into features of LigIV among human DNA ligases.
authors.affiliation: Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, UK. to237@cam.ac.uk.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ochi
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Gu
authors.forename: Tom L
authors.initials: TL
authors.lastname: Blundell
mesh_terms: D002384:Catalysis; D003461:Crystallography; D053903:DNA Breaks, Double-Stranded; D059766:DNA End-Joining Repair / Q000235:genetics*; D000072481:DNA Ligase ATP; D011088:DNA Ligases / Q000737:chemistry* / Q000302:isolation & purification; D004268:DNA-Binding Proteins; D004591:Electrophoresis, Polyacrylamide Gel; D004720:Endonucleases; D006801:Humans; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000737:chemistry* / Q000378:metabolism; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation
chemical_list: D004268:DNA-Binding Proteins; C000607893:LIG4 protein, human; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; C426344:DCLRE1C protein, human; D004720:Endonucleases; D011088:DNA Ligases; D000072481:DNA Ligase ATP