title: Crystal structure of the UvrB dimer: insights into the nature and functioning of the UvrAB damage engagement and UvrB-DNA complexes.
abstract: UvrB has a central role in the highly conserved UvrABC pathway functioning not only as a damage recognition element but also as an essential component of the lesion tracking machinery. While it has been recently confirmed that the tracking assembly comprises a UvrA2B2 heterotetramer, the configurations of the damage engagement and UvrB-DNA handover complexes remain obscure. Here, we present the first crystal structure of a UvrB dimer whose biological significance has been verified using both chemical cross-linking and electron paramagnetic resonance spectroscopy. We demonstrate that this dimeric species stably associates with UvrA and forms a UvrA2B2-DNA complex. Our studies also illustrate how signals are transduced between the ATP and DNA binding sites to generate the helicase activity pivotal to handover and formation of the UvrB2-DNA complex, providing key insights into the configurations of these important repair intermediates.
authors: Department of Biological Sciences, Institute of Structural and Molecular Biology, Crystallography, Birkbeck College, Malet Street, London WC1E 7HX, UK.
authors: Matthew P J
authors: MP
authors: Webster
authors: Rachael
authors: R
authors: Jukes
authors: Vlad S
authors: VS
authors: Zamfir
authors: Christopher W M
authors: CW
authors: Kay
authors: Claire
authors: C
authors: Bagnéris
authors: Tracey
authors: T
authors: Barrett
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D003461:Crystallography; D004247:DNA / Q000737:chemistry*; D004249:DNA Damage; D004265:DNA Helicases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D019281:Dimerization; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D017434:Protein Structure, Tertiary
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D000255:Adenosine Triphosphate; D004247:DNA; D004265:DNA Helicases