7X2A

MERS-CoV spike complex with S41 neutralizing antibody Fab Class1 (1u2d RBD with 1Fab)

Summary for 7X2A

• Entry DOI: 10.2210/pdb7x2a/pdb
• EMDB information: 32963
• Descriptor: MERS-CoV Spike glycoprotein, antibody S41 heavy chain, antibody S41 light chain (3 entities in total)
• Functional Keywords: receptor binding domain, viral protein
• Biological source: Severe acute respiratory syndrome coronavirus 2; More
• Total number of polymer chains: 5
• Total formula weight: 492057.43

Authors

Zeng, J.W.,Zhang, S.Y.,Zhou, H.X.,Wang, X.W. (deposition date: 2022-02-25, release date: 2022-11-09, Last modification date: 2024-10-23)

Primary citation

Zhang, S.,Jia, W.,Zeng, J.,Li, M.,Wang, Z.,Zhou, H.,Zhang, L.,Wang, X.
Cryoelectron microscopy structures of a human neutralizing antibody bound to MERS-CoV spike glycoprotein.
Front Microbiol, 13:988298-988298, 2022

PubMed 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).

PubMed: 36246239
DOI: 10.3389/fmicb.2022.988298

Experimental method

ELECTRON MICROSCOPY (2.49 Å)