EMD-32961
MERS-CoV spike complex with S41 neutralizing antibody Fab Class3 (2u1d RBD with 2Fab)
EMD-32961
Single-particle2.49 Å
Deposition: 25/02/2022Map released: 18/01/2023
Last modified: 09/10/2024
Sample Organism:
Homo sapiens,
Severe acute respiratory syndrome coronavirus 2,
Middle East respiratory syndrome-related coronavirus
Sample: MERS-CoV Spike with S41 Fab
Fitted models: 7x28 (Avg. Q-score: 0.184)
Deposition Authors: Zeng JW, Zhang SY, Zhou HX, Wang XW
Sample: MERS-CoV Spike with S41 Fab
Fitted models: 7x28 (Avg. Q-score: 0.184)
Deposition Authors: Zeng JW, Zhang SY, Zhou HX, Wang XW
Cryoelectron microscopy structures of a human neutralizing antibody bound to MERS-CoV spike glycoprotein.
Zhang S,
Jia W,
Zeng J 
,
Li M,
Wang Z,
Zhou H,
Zhang L,
Wang X
(2022) Front Microbiol , 13 , 988298 - 988298
,
Li M,
Wang Z,
Zhou H,
Zhang L,
Wang X
(2022) Front Microbiol , 13 , 988298 - 988298
Abstract:
Neutralizing monoclonal antibodies (mAbs) against highly pathogenic coronaviruses represent promising candidates for clinical intervention. Here, we isolated a potent neutralizing monoclonal antibody, MERS-S41, from a yeast displayed scFv library using the S protein as a bait. To uncover the neutralization mechanism, we determined structures of MERS-S41 Fab in complex with the trimeric spike glycoprotein by cryoelectron microscopy (cryo-EM). We observed four distinct classes of the complex structure, which showed that the MERS-S41 Fab bound to the "up" receptor binding domain (RBD) with full saturation and also bound to an accessible partially lifted "down" RBD, providing a structural basis for understanding how mAbs bind to trimeric spike glycoproteins. Structure analysis of the epitope and cell surface staining assays demonstrated that virus entry is blocked predominantly by direct competition with the host receptor, dipeptidyl peptidase-4 (DPP4).
Neutralizing monoclonal antibodies (mAbs) against highly pathogenic coronaviruses represent promising candidates for clinical intervention. Here, we isolated a potent neutralizing monoclonal antibody, MERS-S41, from a yeast displayed scFv library using the S protein as a bait. To uncover the neutralization mechanism, we determined structures of MERS-S41 Fab in complex with the trimeric spike glycoprotein by cryoelectron microscopy (cryo-EM). We observed four distinct classes of the complex structure, which showed that the MERS-S41 Fab bound to the "up" receptor binding domain (RBD) with full saturation and also bound to an accessible partially lifted "down" RBD, providing a structural basis for understanding how mAbs bind to trimeric spike glycoproteins. Structure analysis of the epitope and cell surface staining assays demonstrated that virus entry is blocked predominantly by direct competition with the host receptor, dipeptidyl peptidase-4 (DPP4).