X. Xiong, K. Qu, Katarzyna A. Ciazynska, M. Hosmillo, A. Carter, S. Ebrahimi, Zunlong Ke, S. Scheres, L. Bergamaschi, G. Grice, Y. Zhang, John Paul A. Kenneth G. C. Mark Anne Carla Jenny Sherly Bradley Lyons Smith Toshner Elmer Ribeiro Kourampa, J. Bradley, P. Lyons, Kenneth G. C. Smith, M. Toshner, A. Elmer, C. Ribeiro, Jenny Kourampa, Sherly Jose, Jane Kennet, J. Rowlands, A. Meadows, Criona O’Brien, Rebecca J Rastall, Cherry Crucusio, Sarah K. Hewitt, Jane Price, J. Calder, L. Canna, Ashlea Bucke, Hugo Tordesillas, Julie Harris, Valentina Ruffolo, Jason Domingo, B. Graves, H. Butcher, D. Caputo, Emma Le Gresley, B. Dunmore, Jennifer Martin, E. Legchenko, C. Treacy, Christopher Huang, Jennifer H Wood, R. Sutcliffe, J. Hodgson, J. Shih, Stefan Graf, Z. Tong, F. Mescia, Tobias Tilly, Ciara O’Donnell, K. Hunter, L. Pointon, Nicole Pond, Marta Wylot, E. Jones, Stuart Fawke, Ben Bullman, L. Bergamaschi, L. Turner, Isobel Jarvis, Ommar Omarjee, Aloka De Sa, J. Marsden, Ariana Betancourt, Marianne Perera, M. Epping, N. Richoz, G. Bower, Rahul Sharma, F. Nice, O. Huhn, H. Stark, N. Walker, K. Stirrups, Nigel R. Ovington, Eleanor Dewhust, Emily Li, S. Papadia, J. Nathan, S. Baker, L. James, H. Baxendale, I. Goodfellow, R. Doffinger, J. Briggs
Nature Structural & Molecular Biology, 2020
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. The SARS-CoV-2 spike glycoprotein is flexible, and its receptor-binding domain (RBD) fluctuates between open and closed conformations. Disulfide bonds are engineered into the spike ectodomain to lock the RBD in the closed state, leading to a construct with high thermostability.
Cited by 56 publications.
Field of study: Medicine