title: Cooperative assembly of simian virus 40 T-antigen hexamers on functional halves of the replication origin.
abstract: The cofactor ATP stimulates the formation of T-antigen double hexamers on the simian virus 40 core origin of replication (I. A. Mastrangelo, P. V. C. Hough, J. S. Wall, M. Dodson, F. B. Dean, and J. Horwitz, Nature [London] 338:658-662, 1989). We report here the pathway for the assembly of hexamers and double hexamers on the core origin. ATP triggers the cooperative assembly of hexamers on the early and late halves of the origin even when they are completely isolated. Hexamer assembly nucleates at T-antigen recognition pentanucleotides in the early half of the origin. In intact origins, assembly of the first hexamer on the early half of the origin cooperatively stimulates the assembly of a second hexamer on the adjacent late half of the origin. Thus, monomer-monomer and hexamer-hexamer interactions of T antigen, allosterically activated by ATP, constitute two distinct types of cooperative interaction with the origin. Finally, we show that the assembly of T-antigen hexamers on isolated half origins leads to the same array of structural changes that T antigen induces in intact origins. We conclude that the origin is divided into complementary halves that each promote the assembly of functional T-antigen hexamers.
authors.affiliation: Department of Microbiology, State University of New York, Stony Brook 11794-8621.
authors.forename: R E
authors.initials: RE
authors.lastname: Parsons
authors.forename: J E
authors.initials: JE
authors.lastname: Stenger
authors.forename: S
authors.initials: S
authors.lastname: Ray
authors.forename: R
authors.initials: R
authors.lastname: Welker
authors.forename: M E
authors.initials: ME
authors.lastname: Anderson
authors.forename: P
authors.initials: P
authors.lastname: Tegtmeyer
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D000957:Antigens, Viral, Tumor / Q000235:genetics* / Q000276:immunology; D001483:Base Sequence; D002478:Cells, Cultured; D004279:DNA, Viral / Q000737:chemistry; D008969:Molecular Sequence Data; D011487:Protein Conformation; D013539:Simian virus 40 / Q000187:drug effects / Q000235:genetics / Q000254:growth & development / Q000276:immunology*; D014779:Virus Replication / Q000276:immunology*
chemical_list: D000957:Antigens, Viral, Tumor; D004279:DNA, Viral; D000255:Adenosine Triphosphate