title: Structure of the topoisomerase VI-B subunit: implications for type II topoisomerase mechanism and evolution.
abstract: Type IIA and type IIB topoisomerases each possess the ability to pass one DNA duplex through another in an ATP-dependent manner. The role of ATP in the strand passage reaction is poorly understood, particularly for the type IIB (topoisomerase VI) family. We have solved the structure of the ATP-binding subunit of topoisomerase VI (topoVI-B) in two states: an unliganded monomer and a nucleotide-bound dimer. We find that topoVI-B is highly structurally homologous to the entire 40-43 kDa ATPase region of type IIA topoisomerases and MutL proteins. Nucleotide binding to topoVI-B leads to dimerization of the protein and causes dramatic conformational changes within each protomer. Our data demonstrate that type IIA and type IIB topoisomerases have descended from a common ancestor and reveal how ATP turnover generates structural signals in the reactions of both type II topoisomerase families. When combined with the structure of the A subunit to create a picture of the intact topoisomerase VI holoenzyme, the ATP-driven motions of topoVI-B reveal a simple mechanism for strand passage by the type IIB topoisomerases.
authors.affiliation: Department of Molecular and Cellular Biology, University of California, Berkeley, 327 Hildebrand Hall 3206, Berkeley, CA 94720, USA.
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Corbett
authors.forename: James M
authors.initials: JM
authors.lastname: Berger
mesh_terms: D000595:Amino Acid Sequence; D019843:Archaeal Proteins; D018360:Crystallography, X-Ray; D004250:DNA Topoisomerases, Type II / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D019281:Dimerization; D019143:Evolution, Molecular; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D021122:Protein Subunits / Q000737:chemistry; D016944:Sulfolobus / Q000201:enzymology*
chemical_list: D019843:Archaeal Proteins; D021122:Protein Subunits; C105141:DNA topoisomerase VI; D004250:DNA Topoisomerases, Type II