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Cryo-EM of a viral RNA and RNA-protein complex reveals how structural dynamics and novel tRNA mimicry combine to hijack host machinery
bioRxiv - Biophysics Pub Date : 2021-08-29 , DOI: 10.1101/2020.09.18.302638
Steve L. Bonilla , Madeline E. Sherlock , Andrea MacFadden , Jeffrey S. Kieft

Viruses require multifunctional structured RNAs to hijack their host’s biochemistry, but their mechanisms can be obscured by the difficulty of solving conformationally dynamic RNA structures. Using cryo-EM, we visualized the structure of the mysterious viral tRNA-like structure (TLS) from brome mosaic virus (BMV), which affects replication, translation, and genome encapsidation. Structures in isolation and bound to tyrosyl-tRNA synthetase (TyrRS) show that this ∼55 kDa purported tRNA mimic undergoes large conformational rearrangements to bind TyrRS in a form that differs dramatically from tRNA. Our studies reveal how viral RNAs can use a combination of static and dynamic RNA structures to bind host machinery through highly noncanonical interactions and highlights the utility of cryo-EM for visualizing small conformationally dynamic structured RNAs.

中文翻译:

病毒 RNA 和 RNA-蛋白质复合物的冷冻电镜揭示了结构动力学和新型 tRNA 模拟如何结合劫持宿主机器

病毒需要多功能的结构化 RNA 来劫持宿主的生物化学,但​​它们的机制可能会被解析构象动态 RNA 结构的困难所掩盖。使用冷冻电镜,我们可视化了来自雀麦花叶病毒 (BMV) 的神秘病毒 tRNA 样结构 (TLS) 的结构,它会影响复制、翻译和基因组衣壳化。分离并与酪氨酰-tRNA 合成酶 (TyrRS) 结合的结构表明,这种~55 kDa 的 tRNA 模拟物经历了大的构象重排,以与 tRNA 显着不同的形式结合 TyrRS。我们的研究揭示了病毒 RNA 如何使用静态和动态 RNA 结构的组合通过高度非规范的相互作用结合宿主机器,并强调了冷冻电镜在可视化小构象动态结构化 RNA 中的效用。
更新日期:2021-09-01
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