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Structure of the topoisomerase VI‐B subunit: implications for type II topoisomerase mechanism and evolution
Author(s) -
Corbett Kevin D.,
Berger James M.
Publication year - 2003
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdg008
Subject(s) - biology , topoisomerase , protein subunit , mechanism (biology) , genetics , dna , gene , philosophy , epistemology
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.