6NB5

Crystal structure of anti- MERS-CoV human neutralizing LCA60 antibody Fab fragment

Summary for 6NB5

• Entry DOI: 10.2210/pdb6nb5/pdb
• Descriptor: LCA60 antigen-binding (Fab) fragment, heavy chain, LCA60 antigen-binding (Fab) fragment, light chain (2 entities in total)
• Functional Keywords: fab, coronavirus, mers-cov, glycoprotein, structural genomics, seattle structural genomics center for infectious disease, ssgcid, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 94124.91

Authors

Walls, A.J.,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.,Seattle Structural Genomics Center for Infectious Disease (SSGCID) (deposition date: 2018-12-06, release date: 2019-02-06, Last modification date: 2024-10-23)

Primary citation

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.
Unexpected Receptor Functional Mimicry Elucidates Activation of Coronavirus Fusion.
Cell, 176:1026-1039.e15, 2019

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.

PubMed: 30712865
DOI: 10.1016/j.cell.2018.12.028

Experimental method

X-RAY DIFFRACTION (3 Å)