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TitleCryoelectron microscopy structures of a human neutralizing antibody bound to MERS-CoV spike glycoprotein.
Journal, issue, pagesFront Microbiol, Vol. 13, Page 988298, Year 2022
Publish dateSep 28, 2022
AuthorsShuyuan Zhang / Wenxv Jia / Jianwei Zeng / Mingxi Li / Ziyi Wang / Haixia Zhou / Linqi Zhang / Xinquan Wang /
PubMed AbstractNeutralizing 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 linksFront Microbiol / PubMed:36246239 / PubMed Central
MethodsEM (single particle)
Resolution2.49 - 3.685 Å
Structure data

32958

7x25

EMDB-32958, PDB-7x25:
MERS-CoV spike complex with S41 neutralizing antibody Fab Class4 (2u1d RBD with 3Fab)
Method: EM (single particle) / Resolution: 2.49 Å

32959

7x26

EMDB-32959, PDB-7x26:
S41 neutralizing antibody Fab(MERS-CoV)
Method: EM (single particle) / Resolution: 3.685 Å

32961

7x28

EMDB-32961, PDB-7x28:
MERS-CoV spike complex with S41 neutralizing antibody Fab Class3 (2u1d RBD with 2Fab)
Method: EM (single particle) / Resolution: 2.49 Å

32962

7x29

EMDB-32962, PDB-7x29:
MERS-CoV spike complex with S41 neutralizing antibody Fab Class2 (1u2d RBD with 2Fab)
Method: EM (single particle) / Resolution: 2.49 Å

32963

7x2a

EMDB-32963, PDB-7x2a:
MERS-CoV spike complex with S41 neutralizing antibody Fab Class1 (1u2d RBD with 1Fab)
Method: EM (single particle) / Resolution: 2.49 Å

Source
  • severe acute respiratory syndrome coronavirus 2
  • homo sapiens (human)
  • middle east respiratory syndrome-related coronavirus
KeywordsVIRAL PROTEIN / receptor binding domain / VIRAL PROTEIN/IMMUNE SYSTEM / antibody / VIRAL PROTEIN-IMMUNE SYSTEM complex

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