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。
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