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. 2016 Oct;12(10):831-7.
doi: 10.1038/nchembio.2152. Epub 2016 Aug 15.

TALE proteins search DNA using a rotationally decoupled mechanism

Luke Cuculis  1 , Zhanar Abil  2 , Huimin Zhao  1   2   3   4   5 , Charles M Schroeder  1   3   4   5
Affiliations

TALE proteins search DNA using a rotationally decoupled mechanism

Luke Cuculis et al. Nat Chem Biol. 2016 Oct.

Abstract

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.

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