title: DNA recognition via mutual-induced fit by the core-binding domain of bacteriophage lambda integrase.
abstract: Bacteriophage lambda integrase (lambda-Int), a phage-encoded DNA recombinase, cleaves its substrate DNA to facilitate the formation and later resolution of a Holliday junction intermediate during recombination. The core-binding and catalytic domains of lambda-Int constitute a bipartite enzyme that mediates site-specific DNA cleavage through their interactions with opposite sides of the recognition sequence. Despite minimal direct contact between the domains, the core-binding domain has been shown to facilitate site-specific DNA cleavage when provided in trans, indicating that it plays a role beyond enhancing binding affinity. Biophysical characterization of the core-binding domain and its interactions with DNA reveal that the domain is poorly structured in its free form and folds upon binding to DNA. Folding of the protein is accompanied by induced-fit structural changes in the DNA ligand. These data support a model by which the core-binding domain plays a catalytic role by reshaping the substrate DNA for effective cleavage by the catalytic domain.
authors.affiliation: Graduate Program in Biophysics and Department of Biochemistry, The Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: Hari B
authors.initials: HB
authors.lastname: Kamadurai
authors.forename: Mark P
authors.initials: MP
authors.lastname: Foster
mesh_terms: D010582:Bacteriophage lambda / Q000201:enzymology; D002942:Circular Dichroism; D050660:Core Binding Factors / Q000737:chemistry* / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D019426:Integrases / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D013050:Spectrometry, Fluorescence; D013816:Thermodynamics
chemical_list: D050660:Core Binding Factors; D004247:DNA; D019426:Integrases