title: Solution conformations of prototype foamy virus integrase and its stable synaptic complex with U5 viral DNA.
abstract: Using small-angle X-ray and neutron scattering (SAXS/SANS), in combination with analytical centrifugation and light scattering, we have determined the solution properties of PFV IN alone and its synaptic complex with processed U5 viral DNA and related these properties to models derived from available crystal structures. PFV IN is a monomer in solution, and SAXS analysis indicates an ensemble of conformations that differ from that observed in the crystallographic DNA-bound state. Scattering data indicate that the PFV intasome adopts a shape in solution that is consistent with the tetrameric assembly inferred from crystallographic symmetry, and these properties are largely preserved in the presence of divalent ions and clinical strand transfer inhibitors. Using contrast variation methods, we have reconstructed the solution structure of the PFV intasome complex and have located the distal domains of IN that were unresolved by crystallography. These results provide important insights into the architecture of the retroviral intasome.
authors.affiliation: Department of Biochemistry and Biophysics, Perelman School of Medicine and Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia, PA 19104-6059, USA.
authors.forename: Kushol
authors.initials: K
authors.lastname: Gupta
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Curtis
authors.forename: Susan
authors.initials: S
authors.lastname: Krueger
authors.forename: Young
authors.initials: Y
authors.lastname: Hwang
authors.forename: Peter
authors.initials: P
authors.lastname: Cherepanov
authors.forename: Frederic D
authors.initials: FD
authors.lastname: Bushman
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Van Duyne
mesh_terms: D004279:DNA, Viral / Q000378:metabolism*; D019426:Integrases / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D012542:Scattering, Radiation; D016092:Spumavirus / Q000201:enzymology* / Q000235:genetics
chemical_list: D004279:DNA, Viral; D019426:Integrases