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Controllable molecular motors engineered from myosin and RNA
Nature Nanotechnology ( IF 38.3 ) Pub Date :  , DOI: 10.1038/s41565-017-0005-y
Tosan Omabegho , Pinar S. Gurel , Clarence Y. Cheng , Laura Y. Kim , Paul V. Ruijgrok , Rhiju Das , Gregory M. Alushin , Zev Bryant

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.

中文翻译:

由肌球蛋白和RNA设计的可控分子马达

工程生物分子电动机可以提供结构-功能关系和定制组件的直接测试,以控制人造系统1或活细胞2中的分子运输。以前,合成核酸马达3、4、5和修饰的天然蛋白质马达6、7、8、9、10已经在单独的补充策略中得到开发,以实现可调和可控的马达功能。整合蛋白质和核酸成分以形成工程化的核蛋白马达,可以实现其他复杂的功能。然而,这种潜力只是在利用DNA支架来决定拴系蛋白马达的间距,数量和组成的开拓性工作中才开始挖掘的11、12、13、14、15。在这里,我们描述了肌球蛋白电机,它结合了RNA杠杆臂,形成了混合装配,其中蛋白质电机结构域中的构象变化被核酸结构放大和重定向。RNA杠杆臂的几何形状决定了电机运输的速度和方向,可以使用杠杆臂结构7,9中的程序化过渡来动态控制。我们已经使用体外运动分析,单分子跟踪,低温电子显微镜和结构探测16表征了混合动力汽车。我们的设计包括核蛋白马达,可响应驱动链置换的寡核苷酸而可逆地改变方向17反应。在多聚体组装中,可控马达沿着肌动蛋白丝以10–20 nm s -1的速度前进。最后,为了说明多重可寻址控制的潜力,我们证明了RNA变体对寡核苷酸信号的序列特异性反应。
更新日期:2017-11-06
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