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研究揭示穿透蛋白在非包膜病毒上的功能性重折叠
2021-01-17 16:11

美国哈佛医学院Stephen C. Harrison、Simon Jenni等研究人员合作揭示穿透蛋白在非包膜病毒上的功能性重折叠。该研究于2021年1月13日在线发表于国际一流学术期刊《自然》。

据研究人员介绍,非包膜病毒需要膜病灶才能将其基因组传递到靶细胞中。对于轮状病毒,膜穿孔是病毒外层蛋白VP4的主要功能。

通过使用电子冷冻显微术,研究人员确定了VP4如何执行此功能,并表明当被裂解为VP8*和VP5*激活时,VP4可以在病毒体表面上从“直立”重新排列为“反向”构象。反向结构将先前埋藏的“脚”区域向外投射到病毒体已附着的宿主细胞膜中。病毒颗粒进入细胞的冷冻电镜图与该图一致。通过使用VP4的二硫键突变体,研究人员还在两个构象之间的过渡中稳定了可能的中间体。
 
这项研究结果确定了轮状病毒进入靶细胞膜的第一步分子机制,并暗示了与其他病毒的机制相似性。
 
附:英文原文

Title: Functional refolding of the penetration protein on a non-enveloped virus

Author: Tobias Herrmann, Ral Torres, Eric N. Salgado, Cristina Berciu, Daniel Stoddard, Daniela Nicastro, Simon Jenni, Stephen C. Harrison

Issue&Volume: 2021-01-13

Abstract: A non-enveloped virus requires a membrane lesion to deliver its genome into a target cell1. For rotaviruses, membrane perforation is a principal function of the viral outer-layer protein, VP42,3. Here we describe the use of electron cryomicroscopy to determine how VP4 performs this function and show that when activated by cleavage to VP8* and VP5*, VP4 can rearrange on the virion surface from an ‘upright’ to a ‘reversed’ conformation. The reversed structure projects a previously buried ‘foot’ domain outwards into the membrane of the host cell to which the virion has attached. Electron cryotomograms of virus particles entering cells are consistent with this picture. Using a disulfide mutant of VP4, we have also stabilized a probable intermediate in the transition between the two conformations. Our results define molecular mechanisms for the first steps of the penetration of rotaviruses into the membranes of target cells and suggest similarities with mechanisms postulated for other viruses.

DOI: 10.1038/s41586-020-03124-4

Source: https://www.nature.com/articles/s41586-020-03124-4

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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