Download MendeleyUnexpected Receptor Functional Mimicry Elucidates Activation of Coronavirus Fusion.
Walls, A.C., Xiong, X., Park, Y.J., Tortorici, M.A., Snijder, J., Quispe, J., Cameroni, E., Gopal, R., Dai, M., Lanzavecchia, A., Zambon, M., Rey, F.A., Corti, D., Veesler, D.(2019) Cell 176: 1026-1039.e15
- PubMed: 30712865
- DOI: https://doi.org/10.1016/j.cell.2018.12.028
- Primary Citation of Related Structures:
6NB3, 6NB4, 6NB5, 6NB6, 6NB7, 6NB8 - PubMed Abstract:
Recent outbreaks of severe acute respiratory syndrome and Middle East respiratory syndrome, along with the threat of a future coronavirus-mediated pandemic, underscore the importance of finding ways to combat these viruses. The trimeric spike transmembrane glycoprotein S mediates entry into?host cells and is the major target of neutralizing antibodies. To understand the humoral immune response elicited upon natural infections with coronaviruses, we structurally characterized the SARS-CoV and MERS-CoV S glycoproteins in complex with neutralizing antibodies isolated from human survivors. Although the two antibodies studied blocked attachment to the host cell receptor, only the anti-SARS-CoV S antibody triggered fusogenic conformational changes via receptor functional mimicry. These results provide a structural framework for understanding coronavirus neutralization by human antibodies and shed light on activation of coronavirus membrane fusion, which takes place through a receptor-driven ratcheting mechanism.
Organizational Affiliation:
Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA.
