Argonaute bypasses cellular obstacles without hindrance during target search

Thijs Cui, Misha Klein, Jorrit W. Hegge, Stanley D. Chandradoss, John van der Oost, Martin Depken, Chirlmin Joo

Research output: Contribution to journalArticleScientificpeer-review

6 Citations (Scopus)
51 Downloads (Pure)

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.

Original languageEnglish
Article number4390
Number of pages11
JournalNature Communications
Volume10
Issue number1
DOIs
Publication statusPublished - 2019

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