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Controllable molecular motors engineered from myosin and RNA

Engineering biomolecular motors can provide direct tests of structure-function relationships and customized components for controlling molecular transport in artificial systems(1) or in living cells(2). Previously, synthetic nucleic acid motors(3–5) and modified natural protein motors(6–10) have bee...

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Autores principales: Omabegho, Tosan, Gurel, Pinar S., Cheng, Clarence Y., Kim, Laura Y., Ruijgrok, Paul V., Das, Rhiju, Alushin, Gregory M., Bryant, Zev
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5762270/
https://www.ncbi.nlm.nih.gov/pubmed/29109539
http://dx.doi.org/10.1038/s41565-017-0005-y
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author Omabegho, Tosan
Gurel, Pinar S.
Cheng, Clarence Y.
Kim, Laura Y.
Ruijgrok, Paul V.
Das, Rhiju
Alushin, Gregory M.
Bryant, Zev
author_facet Omabegho, Tosan
Gurel, Pinar S.
Cheng, Clarence Y.
Kim, Laura Y.
Ruijgrok, Paul V.
Das, Rhiju
Alushin, Gregory M.
Bryant, Zev
author_sort Omabegho, Tosan
collection PubMed
description Engineering biomolecular motors can provide direct tests of structure-function relationships and customized components for controlling molecular transport in artificial systems(1) or in living cells(2). Previously, synthetic nucleic acid motors(3–5) and modified natural protein motors(6–10) have been developed in separate complementary strategies for achieving tunable and controllable motor function. Integrating protein and nucleic acid components to form engineered nucleoprotein motors may enable additional sophisticated functionalities. However, this potential has only begun to be explored in pioneering work harnessing DNA scaffolds to dictate the spacing, number, and composition of tethered protein motors(11–15). Here, we describe myosin motors that incorporate RNA lever arms, forming hybrid assemblies in which conformational changes in the protein motor domain are amplified and redirected by nucleic acid structures. The RNA lever arm geometry determines the speed and direction of motor transport, and can be dynamically controlled using programmed transitions in lever arm structure(7,9). We have characterized the hybrid motors using in vitro motility assays, single-molecule tracking, cryo-electron microscopy, and structural probing(16). Our designs include nucleoprotein motors that reversibly change direction in response to oligonucleotides that drive strand-displacement(17) reactions. In multimeric assemblies, the controllable motors walk processively along actin filaments at speeds of 10–20 nm s(−1). Finally, to illustrate the potential for multiplexed addressable control, we demonstrate sequence-specific responses of RNA variants to oligonucleotide signals.
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spelling pubmed-57622702018-05-06 Controllable molecular motors engineered from myosin and RNA Omabegho, Tosan Gurel, Pinar S. Cheng, Clarence Y. Kim, Laura Y. Ruijgrok, Paul V. Das, Rhiju Alushin, Gregory M. Bryant, Zev Nat Nanotechnol Article Engineering biomolecular motors can provide direct tests of structure-function relationships and customized components for controlling molecular transport in artificial systems(1) or in living cells(2). Previously, synthetic nucleic acid motors(3–5) and modified natural protein motors(6–10) have been developed in separate complementary strategies for achieving tunable and controllable motor function. Integrating protein and nucleic acid components to form engineered nucleoprotein motors may enable additional sophisticated functionalities. However, this potential has only begun to be explored in pioneering work harnessing DNA scaffolds to dictate the spacing, number, and composition of tethered protein motors(11–15). Here, we describe myosin motors that incorporate RNA lever arms, forming hybrid assemblies in which conformational changes in the protein motor domain are amplified and redirected by nucleic acid structures. The RNA lever arm geometry determines the speed and direction of motor transport, and can be dynamically controlled using programmed transitions in lever arm structure(7,9). We have characterized the hybrid motors using in vitro motility assays, single-molecule tracking, cryo-electron microscopy, and structural probing(16). Our designs include nucleoprotein motors that reversibly change direction in response to oligonucleotides that drive strand-displacement(17) reactions. In multimeric assemblies, the controllable motors walk processively along actin filaments at speeds of 10–20 nm s(−1). Finally, to illustrate the potential for multiplexed addressable control, we demonstrate sequence-specific responses of RNA variants to oligonucleotide signals. 2017-11-06 2018-01 /pmc/articles/PMC5762270/ /pubmed/29109539 http://dx.doi.org/10.1038/s41565-017-0005-y Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms Reprints and permission information is available online at www.nature.com/reprints.
spellingShingle Article
Omabegho, Tosan
Gurel, Pinar S.
Cheng, Clarence Y.
Kim, Laura Y.
Ruijgrok, Paul V.
Das, Rhiju
Alushin, Gregory M.
Bryant, Zev
Controllable molecular motors engineered from myosin and RNA
title Controllable molecular motors engineered from myosin and RNA
title_full Controllable molecular motors engineered from myosin and RNA
title_fullStr Controllable molecular motors engineered from myosin and RNA
title_full_unstemmed Controllable molecular motors engineered from myosin and RNA
title_short Controllable molecular motors engineered from myosin and RNA
title_sort controllable molecular motors engineered from myosin and rna
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5762270/
https://www.ncbi.nlm.nih.gov/pubmed/29109539
http://dx.doi.org/10.1038/s41565-017-0005-y
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