当前位置: X-MOL 学术Nat. Struct. Mol. Biol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Controlling the SARS-CoV-2 spike glycoprotein conformation.
Nature Structural & Molecular Biology ( IF 16.8 ) Pub Date : 2020-07-22 , DOI: 10.1038/s41594-020-0479-4
Rory Henderson 1, 2 , Robert J Edwards 1, 2 , Katayoun Mansouri 1 , Katarzyna Janowska 1 , Victoria Stalls 1 , Sophie M C Gobeil 1 , Megan Kopp 1 , Dapeng Li 1 , Rob Parks 1 , Allen L Hsu 3 , Mario J Borgnia 3 , Barton F Haynes 1, 2, 4 , Priyamvada Acharya 1, 5
Affiliation  

The coronavirus (CoV) spike (S) protein, involved in viral–host cell fusion, is the primary immunogenic target for virus neutralization and the current focus of many vaccine design efforts. The highly flexible S-protein, with its mobile domains, presents a moving target to the immune system. Here, to better understand S-protein mobility, we implemented a structure-based vector analysis of available β-CoV S-protein structures. Despite an overall similarity in domain organization, we found that S-proteins from different β-CoVs display distinct configurations. Based on this analysis, we developed two soluble ectodomain constructs for the SARS-CoV-2 S-protein, in which the highly immunogenic and mobile receptor binding domain (RBD) is either locked in the all-RBDs ‘down’ position or adopts ‘up’ state conformations more readily than the wild-type S-protein. These results demonstrate that the conformation of the S-protein can be controlled via rational design and can provide a framework for the development of engineered CoV S-proteins for vaccine applications.



中文翻译:

控制 SARS-CoV-2 刺突糖蛋白构象。

参与病毒-宿主细胞融合的冠状病毒 (CoV) 刺突 (S) 蛋白是病毒中和的主要免疫原性靶标,也是当前许多疫苗设计工作的重点。高度灵活的 S 蛋白及其移动结构域为免疫系统提供了一个移动目标。在这里,为了更好地了解 S 蛋白的迁移率,我们对可用的 β-CoV S 蛋白结构进行了基于结构的向量分析。尽管域组织总体相似,但我们发现来自不同 β-CoV 的 S 蛋白显示出不同的配置。基于此分析,我们为 SARS-CoV-2 S 蛋白开发了两种可溶性胞外域构建体,其中高度免疫原性和可移动的受体结合域 (RBD) 要么被锁定在所有 RBD 的“向下”位置,要么比野生型 S 蛋白更容易采用“向上”状态构象。这些结果表明,S蛋白的构象可以通过合理的设计来控制,并可以为开发用于疫苗应用的工程化CoV S蛋白提供框架。

更新日期:2020-07-22
down
wechat
bug