Structure of the topoisomerase VI-B subunit: Implications for type II topoisomerase mechanism and evolution

Kevin D. Corbett, James M. Berger

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)151-163
Number of pages13
JournalEMBO Journal
Volume22
Issue number1
DOIs
StatePublished - Jan 2 2003
Externally publishedYes

Keywords

  • ATPase
  • Allostery
  • Archaea
  • DNA-binding protein
  • Topoisomerase

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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