| Literature DB >> 32737467 |
Xiaoli Xiong1, Kun Qu2, Katarzyna A Ciazynska2, Myra Hosmillo3, Andrew P Carter2, Soraya Ebrahimi4, Zunlong Ke2, Sjors H W Scheres2, Laura Bergamaschi5, Guinevere L Grice5, Ying Zhang6,7, James A Nathan5, Stephen Baker5, Leo C James8, Helen E Baxendale9, Ian Goodfellow3, Rainer Doffinger4, John A G Briggs10.
Abstract
The spike (S) protein of SARS-CoV-2 mediates receptor binding and cell entry and is the dominant target of the immune system. It exhibits substantial conformational flexibility. It transitions from closed to open conformations to expose its receptor-binding site and, subsequently, from prefusion to postfusion conformations to mediate fusion of viral and cellular membranes. S-protein derivatives are components of vaccine candidates and diagnostic assays, as well as tools for research into the biology and immunology of SARS-CoV-2. Here we have designed mutations in S that allow the production of thermostable, disulfide-bonded S-protein trimers that are trapped in the closed, prefusion state. Structures of the disulfide-stabilized and non-disulfide-stabilized proteins reveal distinct closed and locked conformations of the S trimer. We demonstrate that the designed, thermostable, closed S trimer can be used in serological assays. This protein has potential applications as a reagent for serology, virology and as an immunogen.Entities:
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Year: 2020 PMID： 32737467 PMCID： PMC7116388 DOI： 10.1038/s41594-020-0478-5
Source DB: PubMed Journal: Nat Struct Mol Biol ISSN： 1545-9985 Impact factor: 15.369