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-Structure paper
Title | Unexpected Receptor Functional Mimicry Elucidates Activation of Coronavirus Fusion. |
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Journal, issue, pages | Cell, Vol. 176, Issue 5, Page 1026-1039.e15, Year 2019 |
Publish date | Feb 21, 2019 |
Authors | Alexandra C Walls / Xiaoli Xiong / Young-Jun Park / M Alejandra Tortorici / Joost Snijder / Joel Quispe / Elisabetta Cameroni / Robin Gopal / Mian Dai / Antonio Lanzavecchia / Maria Zambon / Félix A Rey / Davide Corti / David Veesler / |
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 ...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. |
External links | Cell / PubMed:30712865 / PubMed Central |
Methods | EM (single particle) / X-ray diffraction |
Resolution | 1.5 - 4.5 Å |
Structure data | EMDB-0401, PDB-6nb3: EMDB-0402, PDB-6nb4: EMDB-0403, PDB-6nb6: EMDB-0404, PDB-6nb7: PDB-6nb5: PDB-6nb8: |
Chemicals | ChemComp-NAG: ChemComp-HOH: |
Source |
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Keywords | VIRUS / coronavirus spike glycoprotein / MERS-CoV / SARS-CoV / human neutralizing antibodies / Structural Genomics / Seattle Structural Genomics Center for Infectious Disease / SSGCID / IMMUNE SYSTEM / Fab / Coronavirus / Glycoprotein / SARS |