A thermostable, closed SARS-CoV-2 spike protein trimer

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.

Media Type:

Electronic Article

Year of Publication:

2020

Contained In:

Nature structural & molecular biology - Vol. 27, No. 10 (2020), p. 934-941

Language:

English

Contributors:

Xiong, Xiaoli
Qu, Kun
Ciazynska, Katarzyna A
Hosmillo, Myra
Carter, Andrew P
Ebrahimi, Soraya
Ke, Zunlong
Scheres, Sjors H W
Bergamaschi, Laura
Grice, Guinevere L
Zhang, Ying
CITIID-NIHR COVID-19 BioResource Collaboration
Nathan, James A
Baker, Stephen
James, Leo C
Baxendale, Helen E
Goodfellow, Ian
Doffinger, Rainer
Briggs, John A G
Bradley, John
Lyons, Paul A
Smith, Kenneth G C
Toshner, Mark
Elmer, Anne
Ribeiro, Carla
Kourampa, Jenny
Jose, Sherly
Kennet, Jane
Rowlands, Jane
Meadows, Anne
O'Brien, Criona
Rastall, Rebecca
Crucusio, Cherry
Hewitt, Sarah
Price, Jane
Calder, Jo
Canna, Laura
Bucke, Ashlea
Tordesillas, Hugo
Harris, Julie
Ruffolo, Valentina
Domingo, Jason
Graves, Barbara
Butcher, Helen
Caputo, Daniela
Le Gresley, Emma
Dunmore, Benjamin J
Martin, Jennifer
Legchenko, Ekaterina
Treacy, Carmen
Huang, Christopher
Wood, Jennifer
Sutcliffe, Rachel
Hodgson, Josh
Shih, Joy
Graf, Stefan
Tong, Zhen
Mescia, Federica
Tilly, Tobias
O'Donnell, Ciara
Hunter, Kelvin
Pointon, Linda
Pond, Nicole
Wylot, Marta
Jones, Emma
Fawke, Stuart
Bullman, Ben
Bergamaschi, Laura
Turner, Lori
Jarvis, Isobel
Omarjee, Ommar
De Sa, Aloka
Marsden, Joe
Betancourt, Ariana
Perera, Marianne
Epping, Maddie
Richoz, Nathan
Bower, Georgie
Sharma, Rahul
Nice, Francesca
Huhn, Oisin
Stark, Hannah
Walker, Neil
Stirrups, Kathy
Ovington, Nigel
Dewhust, Eleanor
Li, Emily
Papadia, Sofia

Links:

Volltext

Keywords:

Betacoronavirus
Clinical Laboratory Techniques
Coronavirus Infections
Cryoelectron Microscopy
Disulfides
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
Humans
Immunoglobulin G
Journal Article
Models, Molecular
Mutation
Protein Conformation
Protein Engineering
Protein Multimerization
Protein Stability
Research Support, Non-U.S. Gov't
Spike Glycoprotein, Coronavirus
Spike protein, SARS-CoV-2
Temperature

Notes:

Date Completed 29.10.2020

Date Revised 29.10.2020

published: Print-Electronic

Citation Status MEDLINE

Copyright: From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Physical Description:

Online-Ressource

doi:

10.1038/s41594-020-0478-5

PMID:

32737467

PPN (Catalogue-ID):

NLM314056300