期刊
NATURE STRUCTURAL & MOLECULAR BIOLOGY
卷 27, 期 10, 页码 925-+出版社
NATURE PORTFOLIO
DOI: 10.1038/s41594-020-0479-4
关键词
-
资金
- NIH Common Fund Transformative High Resolution Cryo-Electron Microscopy program [U24 GM129539]
- Simons Foundation [SF349247]
- Integrated Preclinical/Clinical AIDS Vaccine Development Program, NIAID, NIH [U19 AI142596]
- Duke University Center for AIDS Research (CFAR)
- Intramural Research Program of the NIH
- National Institute of Environmental Health Sciences [ZIC ES103326]
- State of North Carolina Pandemic Recovery Office through the Coronavirus Aid, Relief and Economic Security (CARES) Act
- NIH [R01 AI145687]
- Duke Research Computing at Duke University [NIH 1S10OD018164-01]
- NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [ZIAES103341] Funding Source: NIH RePORTER
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 beta-CoV S-protein structures. Despite an overall similarity in domain organization, we found that S-proteins from different beta-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. The SARS-CoV-2 spike glycoprotein is flexible, and its receptor-binding domain (RBD) fluctuates between up or down conformations. Mutations engineered into the spike ectodomain either lock the RBD in the down state or make it adopt the up conformation more readily.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据