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Title | Cryoelectron microscopy structures of a human neutralizing antibody bound to MERS-CoV spike glycoprotein. |
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Journal, issue, pages | Front Microbiol, Vol. 13, Page 988298, Year 2022 |
Publish date | Sep 28, 2022 |
Authors | Shuyuan Zhang / Wenxv Jia / Jianwei Zeng / Mingxi Li / Ziyi Wang / Haixia Zhou / Linqi Zhang / Xinquan Wang / |
PubMed Abstract | Neutralizing monoclonal antibodies (mAbs) against highly pathogenic coronaviruses represent promising candidates for clinical intervention. Here, we isolated a potent neutralizing monoclonal ...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). |
External links | Front Microbiol / PubMed:36246239 / PubMed Central |
Methods | EM (single particle) |
Resolution | 2.49 - 3.685 Å |
Structure data | EMDB-32958, PDB-7x25: EMDB-32959, PDB-7x26: EMDB-32961, PDB-7x28: EMDB-32962, PDB-7x29: EMDB-32963, PDB-7x2a: |
Source |
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Keywords | VIRAL PROTEIN / receptor binding domain / VIRAL PROTEIN/IMMUNE SYSTEM / antibody / VIRAL PROTEIN-IMMUNE SYSTEM complex |