title: Non-homologous end-joining partners in a helical dance: structural studies of XLF-XRCC4 interactions.
abstract: XRCC4 (X-ray cross-complementation group 4) and XLF (XRCC4-like factor) are two essential interacting proteins in the human NHEJ (non-homologous end-joining) pathway that repairs DNA DSBs (double-strand breaks). The individual crystal structures show that the dimeric proteins are homologues with protomers containing head domains and helical coiled-coil tails related by approximate two-fold symmetry. Biochemical, mutagenesis, biophysical and structural studies have identified the regions of interaction between the two proteins and suggested models for the XLF-XRCC4 complex. An 8.5 Å (1 Å = 0.1 nm) resolution crystal structure of XLF-XRCC4 solved by molecular replacement, together with gel filtration and nano-ESI (nano-electrospray ionization)-MS results, demonstrates that XLF and XRCC4 dimers interact through their head domains and form an alternating left-handed helical structure with polypeptide coiled coils and pseudo-dyads of individual XLF and XRCC4 dimers at right angles to the helical axis.
authors.affiliation: Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1GA, UK. qw222@cam.ac.uk
authors.forename: Qian
authors.initials: Q
authors.lastname: Wu
authors.forename: Takashi
authors.initials: T
authors.lastname: Ochi
authors.forename: Dijana
authors.initials: D
authors.lastname: Matak-Vinkovic
authors.forename: Carol V
authors.initials: CV
authors.lastname: Robinson
authors.forename: Dimitri Y
authors.initials: DY
authors.lastname: Chirgadze
authors.forename: Tom L
authors.initials: TL
authors.lastname: Blundell
mesh_terms: D003460:Crystallization; D004247:DNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D059766:DNA End-Joining Repair; D011088:DNA Ligases / Q000378:metabolism; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D019281:Dimerization; D006801:Humans; D008958:Models, Molecular; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary
chemical_list: D004268:DNA-Binding Proteins; C508551:NHEJ1 protein, human; C101467:XRCC4 protein, human; D004247:DNA; D011088:DNA Ligases; D045643:DNA Repair Enzymes