论文标题：High-resolution small RNA structures from exact nuclear Overhauser enhancement measurements without additional restraints

期刊：Communications Biology

作者：Parker J. Nichols

发表时间：2018/06/07

数字识别码：10.1038/s42003-018-0067-x

原文链接：https://www.nature.com/articles/s42003-018-0067-x?utm_source=Other_website&utm_medium=Website_links&utm_content=RenLi-Nature-Communications_Biology-Structural_Biology-China&utm_campaign=NEWCOMMS_USG_JRCN_RL_sciencenet_NOE_Aug_3rd

RNA曾被视为结构静止的和只有蛋白质翻译的单项功能生物机器。而近年的研究发现细胞里RNA的表达量不但远远超过了蛋白质，而且RNA在复杂的生物中比如人类等，具有蛋白质的组装，对反应的酶促催化，信号的传递，和控制基因的表达等多种功能。

RNA的生物功能显示了它作为药物靶点的潜力。RNA的序列影响了它的结构和特征，而它的动态结构决定了其功能。所以在原子层面上研究RNA的动态结构会对抑制RNA功能的小分子药物的设计有帮助。

X射线结晶学和冷冻电镜适合研究大型RNA和蛋白质的组合，而核磁共振适合用来研究RNA的结构，小RNA之间，和小RNA与蛋白质之间的动态关系。然而核磁共振仍有很多短板。成分，结构和环境的多样性能帮助RNA的结构的推算。但是RNA只有四种分子成分，所以导致了质子密度低，光谱上的重复，和推算上的困难。由于大多的RNA是A型螺旋，所以在没有发夹环，突起或内环等非典型结构时，结构和环境的多样性也受到了限制。

近日在《通讯-生物学》发表的名为High-resolution small RNA structures from exact nuclear Overhauser enhancement measurements without additional restraints的研究里，科罗拉多大学丹佛分校的安舒茨医学校园的Beat Vögeli的团队试图改进核磁共振在奥弗豪塞尔核效应（NOE）在不同类型的质子空间的距离的计算中的应用。现今NOE数据的质量难以让研究者只依靠它来计算高分辨率的RNA的结构；他们还需要同时参考其他数据。以前Vögeli的团队已经发展了一个用NOE来计算蛋白质里的原子之间的距离（5埃之内，少于0.1埃的误差）的方法。在这里，他们把同样的方法应用到计算RNA里的质子之间的距离，并显示可以在没有其他依据的情况下准确地计算出一个14肽UUCG的发夹结构的高分辨率的结构。还有，他们用同样的NOE方法算出了一个有两个状态的RNA结构。作者们认为，此程序能帮助研究者在计算RNA结构时达到更高的分辨率。

摘要：RNA not only translates the genetic code into proteins, but also carries out important cellular functions. Understanding such functions requires knowledge of the structure and dynamics at atomic resolution. Almost half of the published RNA structures have been solved by nuclear magnetic resonance (NMR). However, as a result of severe resonance overlap and low proton density, high-resolution RNA structures are rarely obtained from nuclear Overhauser enhancement (NOE) data alone. Instead, additional semi-empirical restraints and labor-intensive techniques are required for structural averages, while there are only a few experimentally derived ensembles representing dynamics. Here we show that our exact NOE (eNOE) based structure determination protocol is able to define a 14-mer UUCG tetraloop structure at high resolution without other restraints. Additionally, we use eNOEs to calculate a two-state structure, which samples its conformational space. The protocol may open an avenue to obtain high-resolution structures of small RNA of unprecedented accuracy with moderate experimental efforts.

阅读论文全文请访问：https://www.nature.com/articles/s42003-018-0067-x?utm_source=Other_website&utm_medium=Website_links&utm_content=RenLi-Nature-Communications_Biology-Structural_Biology-China&utm_campaign=NEWCOMMS_USG_JRCN_RL_sciencenet_NOE_Aug_3rd

期刊介绍：Communications Biology is an open access journal from Nature Research publishing high-quality research, reviews and commentary in all areas of the biological sciences. Research papers published by the journal represent significant advances bringing new biological insight to a specialized area of research.

（来源：科学网）