Argonaute bypasses cellular obstacles without hindrance during target search

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 n...

Descripción completa

Detalles Bibliográficos
Autores principales: Cui, Tao Ju, Klein, Misha, Hegge, Jorrit W., Chandradoss, Stanley D., van der Oost, John, Depken, Martin, Joo, Chirlmin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6763497/
https://www.ncbi.nlm.nih.gov/pubmed/31558728
http://dx.doi.org/10.1038/s41467-019-12415-y
_version_ 1783454210543583232
author Cui, Tao Ju
Klein, Misha
Hegge, Jorrit W.
Chandradoss, Stanley D.
van der Oost, John
Depken, Martin
Joo, Chirlmin
author_facet Cui, Tao Ju
Klein, Misha
Hegge, Jorrit W.
Chandradoss, Stanley D.
van der Oost, John
Depken, Martin
Joo, Chirlmin
author_sort Cui, Tao Ju
collection PubMed
description 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.
format Online
Article
Text
id pubmed-6763497
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-67634972019-09-30 Argonaute bypasses cellular obstacles without hindrance during target search Cui, Tao Ju Klein, Misha Hegge, Jorrit W. Chandradoss, Stanley D. van der Oost, John Depken, Martin Joo, Chirlmin Nat Commun Article 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. Nature Publishing Group UK 2019-09-26 /pmc/articles/PMC6763497/ /pubmed/31558728 http://dx.doi.org/10.1038/s41467-019-12415-y Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Cui, Tao Ju
Klein, Misha
Hegge, Jorrit W.
Chandradoss, Stanley D.
van der Oost, John
Depken, Martin
Joo, Chirlmin
Argonaute bypasses cellular obstacles without hindrance during target search
title Argonaute bypasses cellular obstacles without hindrance during target search
title_full Argonaute bypasses cellular obstacles without hindrance during target search
title_fullStr Argonaute bypasses cellular obstacles without hindrance during target search
title_full_unstemmed Argonaute bypasses cellular obstacles without hindrance during target search
title_short Argonaute bypasses cellular obstacles without hindrance during target search
title_sort argonaute bypasses cellular obstacles without hindrance during target search
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6763497/
https://www.ncbi.nlm.nih.gov/pubmed/31558728
http://dx.doi.org/10.1038/s41467-019-12415-y
work_keys_str_mv AT cuitaoju argonautebypassescellularobstacleswithouthindranceduringtargetsearch
AT kleinmisha argonautebypassescellularobstacleswithouthindranceduringtargetsearch
AT heggejorritw argonautebypassescellularobstacleswithouthindranceduringtargetsearch
AT chandradossstanleyd argonautebypassescellularobstacleswithouthindranceduringtargetsearch
AT vanderoostjohn argonautebypassescellularobstacleswithouthindranceduringtargetsearch
AT depkenmartin argonautebypassescellularobstacleswithouthindranceduringtargetsearch
AT joochirlmin argonautebypassescellularobstacleswithouthindranceduringtargetsearch

Ejemplares similares