Jake M. Peterson, Scott T. Becker, Collin A. O’Leary, Puneet Juneja, Yang Yang and Walter N. Moss*,
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引用次数: 0
摘要
严重急性呼吸系统综合征冠状病毒 2(SARS-CoV-2)的移帧刺激元件(FSE)是程序化-1 核糖体移帧(-1 PRF)和优化病毒效力所必需的。FSE 有大量依赖于上下文的交替构象,但其中对-1 PRF 最关键的两个结构是一个衰减发夹和一个三茎 H 型假结结构。仅假结的晶体结构就以螺旋堆叠的线性结构中的三个 RNA 茎为特征,而包括上游七聚体滑动位点在内的 6.9 Å Cryo-EM 结构则导致两个茎之间的弯曲。我们之前的研究暗示了一个扩展的上游多分支环,其中包括衰减器发夹和滑动位点--这是一种之前未建模的构象。我们的目的是通过计算和中分辨率冷冻电镜方法,提供一个 6.1 Å 的冷冻电镜结构,以线性假结结构和动态上游多分支环路为特征,进一步说明 SARS-CoV-2 FSE 的来龙去脉。
Structure of the SARS-CoV-2 Frameshift Stimulatory Element with an Upstream Multibranch Loop
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) frameshift stimulatory element (FSE) is necessary for programmed −1 ribosomal frameshifting (−1 PRF) and optimized viral efficacy. The FSE has an abundance of context-dependent alternate conformations, but two of the structures most crucial to −1 PRF are an attenuator hairpin and a three-stem H-type pseudoknot structure. A crystal structure of the pseudoknot alone features three RNA stems in a helically stacked linear structure, whereas a 6.9 Å cryo-EM structure including the upstream heptameric slippery site resulted in a bend between two stems. Our previous research alluded to an extended upstream multibranch loop that includes both the attenuator hairpin and the slippery site–a conformation not previously modeled. We aim to provide further context to the SARS-CoV-2 FSE via computational and medium resolution cryo-EM approaches, by presenting a 6.1 Å cryo-EM structure featuring a linear pseudoknot structure and a dynamic upstream multibranch loop.
期刊介绍:
Biochemistry provides an international forum for publishing exceptional, rigorous, high-impact research across all of biological chemistry. This broad scope includes studies on the chemical, physical, mechanistic, and/or structural basis of biological or cell function, and encompasses the fields of chemical biology, synthetic biology, disease biology, cell biology, nucleic acid biology, neuroscience, structural biology, and biophysics. In addition to traditional Research Articles, Biochemistry also publishes Communications, Viewpoints, and Perspectives, as well as From the Bench articles that report new methods of particular interest to the biological chemistry community.