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Novel Insights into Guide RNA 5′-Nucleoside/Tide Binding by Human Argonaute 2
The human Argonaute 2 (hAgo2) protein is a key player of RNA interference (RNAi). Upon complex formation with small non-coding RNAs, the protein initially interacts with the 5′-end of a given guide RNA through multiple interactions within the MID domain. This interaction has been reported to show a...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4730269/ https://www.ncbi.nlm.nih.gov/pubmed/26712743 http://dx.doi.org/10.3390/ijms17010022 |
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author | Kalia, Munishikha Willkomm, Sarah Claussen, Jens Christian Restle, Tobias Bonvin, Alexandre M. J. J. |
author_facet | Kalia, Munishikha Willkomm, Sarah Claussen, Jens Christian Restle, Tobias Bonvin, Alexandre M. J. J. |
author_sort | Kalia, Munishikha |
collection | PubMed |
description | The human Argonaute 2 (hAgo2) protein is a key player of RNA interference (RNAi). Upon complex formation with small non-coding RNAs, the protein initially interacts with the 5′-end of a given guide RNA through multiple interactions within the MID domain. This interaction has been reported to show a strong bias for U and A over C and G at the 5′-position. Performing molecular dynamics simulations of binary hAgo2/OH–guide–RNA complexes, we show that hAgo2 is a highly flexible protein capable of binding to guide strands with all four possible 5′-bases. Especially, in the case of C and G this is associated with rather large individual conformational rearrangements affecting the MID, PAZ and even the N-terminal domains to different degrees. Moreover, a 5′-G induces domain motions in the protein, which trigger a previously unreported interaction between the 5′-base and the L2 linker domain. Combining our in silico analyses with biochemical studies of recombinant hAgo2, we find that, contrary to previous observations, hAgo2 is capable of functionally accommodating guide strands regardless of the 5′-base. |
format | Online Article Text |
id | pubmed-4730269 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-47302692016-02-11 Novel Insights into Guide RNA 5′-Nucleoside/Tide Binding by Human Argonaute 2 Kalia, Munishikha Willkomm, Sarah Claussen, Jens Christian Restle, Tobias Bonvin, Alexandre M. J. J. Int J Mol Sci Article The human Argonaute 2 (hAgo2) protein is a key player of RNA interference (RNAi). Upon complex formation with small non-coding RNAs, the protein initially interacts with the 5′-end of a given guide RNA through multiple interactions within the MID domain. This interaction has been reported to show a strong bias for U and A over C and G at the 5′-position. Performing molecular dynamics simulations of binary hAgo2/OH–guide–RNA complexes, we show that hAgo2 is a highly flexible protein capable of binding to guide strands with all four possible 5′-bases. Especially, in the case of C and G this is associated with rather large individual conformational rearrangements affecting the MID, PAZ and even the N-terminal domains to different degrees. Moreover, a 5′-G induces domain motions in the protein, which trigger a previously unreported interaction between the 5′-base and the L2 linker domain. Combining our in silico analyses with biochemical studies of recombinant hAgo2, we find that, contrary to previous observations, hAgo2 is capable of functionally accommodating guide strands regardless of the 5′-base. MDPI 2015-12-24 /pmc/articles/PMC4730269/ /pubmed/26712743 http://dx.doi.org/10.3390/ijms17010022 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons by Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Kalia, Munishikha Willkomm, Sarah Claussen, Jens Christian Restle, Tobias Bonvin, Alexandre M. J. J. Novel Insights into Guide RNA 5′-Nucleoside/Tide Binding by Human Argonaute 2 |
title | Novel Insights into Guide RNA 5′-Nucleoside/Tide Binding by Human Argonaute 2 |
title_full | Novel Insights into Guide RNA 5′-Nucleoside/Tide Binding by Human Argonaute 2 |
title_fullStr | Novel Insights into Guide RNA 5′-Nucleoside/Tide Binding by Human Argonaute 2 |
title_full_unstemmed | Novel Insights into Guide RNA 5′-Nucleoside/Tide Binding by Human Argonaute 2 |
title_short | Novel Insights into Guide RNA 5′-Nucleoside/Tide Binding by Human Argonaute 2 |
title_sort | novel insights into guide rna 5′-nucleoside/tide binding by human argonaute 2 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4730269/ https://www.ncbi.nlm.nih.gov/pubmed/26712743 http://dx.doi.org/10.3390/ijms17010022 |
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