Du Pont Kelly E, McCullagh Martin, Geiss Brian J
Department of Chemistry, Colorado State University, Fort Collins, Colorado, USA.
Department of Chemistry, Oklahoma State University, Stillwater, Oklahoma, USA.
Wiley Interdiscip Rev RNA. 2022 Mar;13(2):e1688. doi: 10.1002/wrna.1688. Epub 2021 Sep 2.
Flaviviruses are a major health concern because over half of the world population is at risk of infection and there are very few antiviral therapeutics to treat diseases resulting from infection. Replication is an essential part of the flavivirus survival. One of the viral proteins, NS3 helicase, is critical for unwinding the double stranded RNA intermediate during flaviviral replication. The helicase performs the unwinding of the viral RNA intermediate structure in an ATP-dependent manner. NS3 helicase is a member of the Viral/DEAH-like subfamily of the superfamily 2 helicase containing eight highly conserved structural motifs (I, Ia, II, III, IV, IVa, V, and VI) localized between the ATP-binding and RNA-binding pockets. Of these structural motifs only three are well characterized for function in flaviviruses (I, II, and VI). The roles of the other structural motifs are not well understood for NS3 helicase function, but comparison of NS3 with other superfamily 2 helicases within the viral/DEAH-like, DEAH/RHA, and DEAD-box subfamilies can be used to elucidate the roles of these structural motifs in the flavivirus NS3 helicase. This review aims to summarize the role of each conserved structural motif within flavivirus NS3 in RNA helicase function. This article is categorized under: RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications RNA in Disease and Development > RNA in Disease.
黄病毒是一个主要的健康问题，因为世界上超过一半的人口有感染风险，而且治疗感染所致疾病的抗病毒疗法非常少。复制是黄病毒生存的一个重要部分。病毒蛋白之一的NS3解旋酶，对于在黄病毒复制过程中解开双链RNA中间体至关重要。该解旋酶以ATP依赖的方式解开病毒RNA中间体结构。NS3解旋酶是超家族2解旋酶的病毒/DEAH样亚家族的成员，包含八个高度保守的结构基序（I、Ia、II、III、IV、IVa、V和VI），位于ATP结合口袋和RNA结合口袋之间。在这些结构基序中，只有三个在黄病毒中的功能得到了很好的表征（I、II和VI）。对于NS3解旋酶的功能，其他结构基序的作用还不太清楚，但将NS3与病毒/DEAH样、DEAH/RHA和DEAD-box亚家族中的其他超家族2解旋酶进行比较，可以用来阐明这些结构基序在黄病毒NS3解旋酶中的作用。本综述旨在总结黄病毒NS3中每个保守结构基序在RNA解旋酶功能中的作用。本文分类如下：RNA与蛋白质及其他分子的相互作用>蛋白质-RNA相互作用：功能影响；疾病与发育中的RNA>疾病中的RNA。
