TY - JOUR
T1 - A thermostable, closed SARS-CoV-2 spike protein trimer
AU - The CITIID-NIHR COVID-19 BioResource Collaboration
AU - Xiong, Xiaoli
AU - Qu, Kun
AU - Ciazynska, Katarzyna A.
AU - Hosmillo, Myra
AU - Carter, Andrew P.
AU - Ebrahimi, Soraya
AU - Ke, Zunlong
AU - Scheres, Sjors H.W.
AU - Bergamaschi, Laura
AU - Grice, Guinevere L.
AU - Zhang, Ying
AU - Bradley, John
AU - Lyons, Paul A.
AU - Smith, Kenneth G.C.
AU - Toshner, Mark
AU - Elmer, Anne
AU - Ribeiro, Carla
AU - Kourampa, Jenny
AU - Jose, Sherly
AU - Kennet, Jane
AU - Rowlands, Jane
AU - Meadows, Anne
AU - O’Brien, Criona
AU - Rastall, Rebecca
AU - Crucusio, Cherry
AU - Hewitt, Sarah
AU - Price, Jane
AU - Calder, Jo
AU - Canna, Laura
AU - Bucke, Ashlea
AU - Tordesillas, Hugo
AU - Harris, Julie
AU - Ruffolo, Valentina
AU - Domingo, Jason
AU - Graves, Barbara
AU - Butcher, Helen
AU - Caputo, Daniela
AU - Le Gresley, Emma
AU - Dunmore, Benjamin J.
AU - Martin, Jennifer
AU - Legchenko, Ekaterina
AU - Treacy, Carmen
AU - Huang, Christopher
AU - Wood, Jennifer
AU - Sutcliffe, Rachel
AU - Hodgson, Josh
AU - Shih, Joy
AU - Graf, Stefan
AU - Tong, Zhen
AU - Mescia, Federica
N1 - Publisher Copyright:
© 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2020/10/1
Y1 - 2020/10/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85089097143&partnerID=8YFLogxK
U2 - 10.1038/s41594-020-0478-5
DO - 10.1038/s41594-020-0478-5
M3 - Article
C2 - 32737467
AN - SCOPUS:85089097143
SN - 1545-9993
VL - 27
SP - 934
EP - 941
JO - Nature Structural and Molecular Biology
JF - Nature Structural and Molecular Biology
IS - 10
ER -