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诺雅病毒结构的 2.7Å 分辨率及对受体结合、衣壳稳定性和分类学的影响。

Structure of Nora virus at 2.7 Å resolution and implications for receptor binding, capsid stability and taxonomy.

机构信息

HiLIFE-Institute of Biotechnology, University of Helsinki, Viikinkaari 9, P.O. Box 56, 00014, Helsinki, Finland.

Molecular and Integrative Biosciences Research Programme, Faculty of Biological and Environmental Sciences, University of Helsinki, Viikinkaari 9, P.O. Box 56, 00014, Helsinki, Finland.

出版信息

Sci Rep. 2020 Nov 12;10(1):19675. doi: 10.1038/s41598-020-76613-1.

DOI:10.1038/s41598-020-76613-1
PMID:33184473
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7661533/
Abstract

Nora virus, a virus of Drosophila, encapsidates one of the largest single-stranded RNA virus genomes known. Its taxonomic affinity is uncertain as it has a picornavirus-like cassette of enzymes for virus replication, but the capsid structure was at the time for genome publication unknown. By solving the structure of the virus, and through sequence comparison, we clear up this taxonomic ambiguity in the invertebrate RNA virosphere. Despite the lack of detectable similarity in the amino acid sequences, the 2.7 Å resolution cryoEM map showed Nora virus to have T = 1 symmetry with the characteristic capsid protein β-barrels found in all the viruses in the Picornavirales order. Strikingly, α-helical bundles formed from the extended C-termini of capsid protein VP4B and VP4C protrude from the capsid surface. They are similar to signalling molecule folds and implicated in virus entry. Unlike other viruses of Picornavirales, no intra-pentamer stabilizing annulus was seen, instead the intra-pentamer stability comes from the interaction of VP4C and VP4B N-termini. Finally, intertwining of the N-termini of two-fold symmetry-related VP4A capsid proteins and RNA, provides inter-pentamer stability. Based on its distinct structural elements and the genetic distance to other picorna-like viruses we propose that Nora virus, and a small group of related viruses, should have its own family within the order Picornavirales.

摘要

诺拉病毒,一种果蝇病毒,包裹着已知最大的单链 RNA 病毒基因组之一。由于其具有类似微小 RNA 病毒的酶类复制病毒的盒,因此其分类学亲缘关系不确定,但当时未知其衣壳结构。通过解决病毒的结构以及通过序列比较,我们澄清了无脊椎动物 RNA 病毒圈内的这种分类学上的模棱两可。尽管在氨基酸序列中没有可检测到的相似性,但 2.7 Å 分辨率的冷冻电镜图谱显示,诺拉病毒具有 T = 1 对称性,所有小 RNA 病毒目中的病毒都具有特征性的衣壳蛋白 β-桶。引人注目的是,衣壳蛋白 VP4B 和 VP4C 的延伸 C 末端形成的α-螺旋束从衣壳表面突出。它们类似于信号分子折叠,并暗示病毒进入。与小 RNA 病毒科的其他病毒不同,没有看到五聚体内部稳定的环,而是五聚体内部的稳定性来自 VP4C 和 VP4B N 末端的相互作用。最后,两个二倍体相关的 VP4A 衣壳蛋白的 N 末端和 RNA 的缠绕提供了五聚体之间的稳定性。基于其独特的结构元素和与其他微小 RNA 样病毒的遗传距离,我们建议诺拉病毒和一小群相关病毒应该在小 RNA 病毒科中拥有自己的家族。

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