Fiche publication
Date publication
septembre 2013
Auteurs
Membres identifiés du Cancéropôle Est :
Dr SCHULTZ Patrick
Tous les auteurs :
Papillon J, Menetret JF, Batisse C, Helye R, Schultz P, Potier N, Lamour V
Lien Pubmed
Résumé
Type 2A DNA topoisomerases (Topo2A) remodel DNA topology during replication, transcription and chromosome segregation. These multisubunit enzymes catalyze the transport of a double-stranded DNA through a transient break formed in another duplex. The bacterial DNA gyrase, a target for broad-spectrum antibiotics, is the sole Topo2A enzyme able to introduce negative supercoils. We reveal here for the first time the architecture of the full-length Thermus thermophilus DNA gyrase alone and in a cleavage complex with a 155 bp DNA duplex in the presence of the antibiotic ciprofloxacin, using cryo-electron microscopy. The structural organization of the subunits of the full-length DNA gyrase points to a central role of the ATPase domain acting like a 'crossover trap' that may help to sequester the DNA positive crossover before strand passage. Our structural data unveil how DNA is asymmetrically wrapped around the gyrase-specific C-terminal beta-pinwheel domains and guided to introduce negative supercoils through cooperativity between the ATPase and beta-pinwheel domains. The overall conformation of the drug-induced DNA binding-cleavage complex also suggests that ciprofloxacin traps a DNA pre-transport conformation.
Référence
Nucleic Acids Res. 2013 Sep;41(16):7815-27
