Transcription activator-like effector (TALE) proteins are a class of programmable DNA-binding proteins used extensively for gene editing. Despite recent progress, however, little is known about their sequence search mechanism. Here, we use single-molecule experiments to study TALE search along DNA. Our results show that TALEs utilize a rotationally decoupled mechanism for nonspecific search, despite remaining associated with DNA templates during the search process. Our results suggest that the protein helical structure enables TALEs to adopt a loosely wrapped conformation around DNA templates during nonspecific search, facilitating rapid one-dimensional (1D) diffusion under a range of solution conditions. Furthermore, this model is consistent with a previously reported two-state mechanism for TALE search that allows these proteins to overcome the search speed-stability paradox. Taken together, our results suggest that TALE search is unique among the broad class of sequence-specific DNA-binding proteins and supports efficient 1D search along DNA.

Original languageEnglish (US)
Pages (from-to)831-837
Number of pages7
JournalNature chemical biology
Issue number10
StatePublished - Oct 1 2016

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


Dive into the research topics of 'TALE proteins search DNA using a rotationally decoupled mechanism'. Together they form a unique fingerprint.

Cite this