Conformational toggling controls target site choice for the heteromeric transposase element Tn7 Academic Article uri icon

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  • The bacterial transposon Tn7 facilitates horizontal transfer by directing transposition into actively replicating DNA with the element-encoded protein TnsE. Structural analysis of the C-terminal domain of wild-type TnsE identified a novel protein fold including a central V-shaped loop that toggles between two distinct conformations. The structure of a robust TnsE gain-of-activity variant has this loop locked in a single conformation, suggesting that conformational flexibility regulates TnsE activity. Structure-based analysis of a series of TnsE mutants relates transposition activity to DNA binding stability. Wild-type TnsE appears to naturally form an unstable complex with a target DNA, whereas mutant combinations required for large changes in transposition frequency and targeting stabilized this interaction. Collectively, our work unveils a unique structural proofreading mechanism where toggling between two conformations regulates target commitment by limiting the stability of target DNA engagement until an appropriate insertion site is identified.


  • Guarne, Alba
  • Shi, Qiaojuan
  • Straus, Marco R
  • Caron, Jeremy J
  • Wang, Huasheng
  • Chung, Yu Seon
  • Guarné, Alba
  • Peters, Joseph E

publication date

  • December 15, 2015