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Argonaute bypasses cellular obstacles without hindrance during target search

Author

Listed:
  • Tao Ju Cui

    (Delft University of Technology)

  • Misha Klein

    (Delft University of Technology)

  • Jorrit W. Hegge

    (Wageningen University)

  • Stanley D. Chandradoss

    (Delft University of Technology
    Oxford NanoImaging)

  • John Oost

    (Wageningen University)

  • Martin Depken

    (Delft University of Technology)

  • Chirlmin Joo

    (Delft University of Technology)

Abstract

Argonaute (Ago) proteins are key players in both gene regulation (eukaryotes) and host defense (prokaryotes). Acting on single-stranded nucleic-acid substrates, Ago relies on base pairing between a small nucleic-acid guide and its complementary target sequences for specificity. To efficiently scan nucleic-acid chains for targets, Ago diffuses laterally along the substrate and must bypass secondary structures as well as protein barriers. Using single-molecule FRET in conjunction with kinetic modelling, we reveal that target scanning is mediated through loose protein-nucleic acid interactions, allowing Ago to slide short distances over secondary structures, as well as to bypass protein barriers via intersegmental transfer. Our combined single-molecule experiment and kinetic modelling approach may serve as a platform to dissect search processes and study the effect of sequence on search kinetics for other nucleic acid-guided proteins.

Suggested Citation

  • Tao Ju Cui & Misha Klein & Jorrit W. Hegge & Stanley D. Chandradoss & John Oost & Martin Depken & Chirlmin Joo, 2019. "Argonaute bypasses cellular obstacles without hindrance during target search," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
  • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12415-y
    DOI: 10.1038/s41467-019-12415-y
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