Abstract
Engineering biomolecular motors can provide direct tests of structure–function relationships and customized components for controlling molecular transport in artificial systems1 or in living cells2. Previously, synthetic nucleic acid motors3,4,5 and modified natural protein motors6,7,8,9,10 have been developed in separate complementary strategies to achieve 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 motors11,12,13,14,15. 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 the lever arm structure7,9. We have characterized the hybrid motors using in vitro motility assays, single-molecule tracking, cryo-electron microscopy and structural probing16. Our designs include nucleoprotein motors that reversibly change direction in response to oligonucleotides that drive strand-displacement17 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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Change history
02 March 2018
An incorrect Supplementary Information file was originally published. The file has been replaced with the correct one.
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Acknowledgements
The authors thank M. Nakamura, T. Schindler, H. Ennomani and other members of the Bryant laboratory for discussions and assistance. This work was supported by a National Institutes of Health (NIH) Fellowship F32GM09442 to T.O., the Division of Intramural Research of the National Heart, Lung, and Blood Institute (G.A.), a Women & Science Fellowship from the Rockefeller University (to P.G.), a Human Frontiers Science Program Long-Term Fellowship (to P.V.R.), NIH High-Risk Research Grants 1DP2 OD004690 (to Z.B.) and 7DP5OD17885 (to G.A.), NIH R01 Grants GM100953 and GM102519 (to R.D.) and a grant from the W.M. Keck Foundation to Manu Prakash and Z.B.
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T.O. and Z.B. conceived the project. T.O. designed molecules, performed research and analysed data. P.S.G. and L.Y.K. performed cryo-EM research. P.S.G. analysed cryo-EM data. C.Y.C. performed MOHCA-seq research and analysed data. P.V.R. performed research and contributed methods. Z.B., G.M.A. and R.D. supervised research. T.O., Z.B., P.S.G., G.M.A. and C.Y.C. wrote the manuscript. All authors provided expertise, discussed the results and commented on the manuscript.
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A correction to this article is available online at https://doi.org/10.1038/s41565-017-0028-4.
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Omabegho, T., Gurel, P.S., Cheng, C.Y. et al. Controllable molecular motors engineered from myosin and RNA. Nature Nanotech 13, 34–40 (2018). https://doi.org/10.1038/s41565-017-0005-y
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DOI: https://doi.org/10.1038/s41565-017-0005-y
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