+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-32959 | |||||||||
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Title | S41 neutralizing antibody Fab(MERS-CoV) | |||||||||
Map data | ||||||||||
Sample |
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Keywords | antibody / VIRAL PROTEIN-IMMUNE SYSTEM complex | |||||||||
Function / homology | Function and homology information endocytosis involved in viral entry into host cell / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / receptor-mediated virion attachment to host cell / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / host cell plasma membrane / virion membrane / membrane Similarity search - Function | |||||||||
Biological species | Severe acute respiratory syndrome coronavirus 2 / Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.685 Å | |||||||||
Authors | Zeng JW / Zhang SY | |||||||||
Funding support | China, 1 items
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Citation | Journal: Front Microbiol / Year: 2022 Title: Cryoelectron microscopy structures of a human neutralizing antibody bound to MERS-CoV spike glycoprotein. Authors: Shuyuan Zhang / Wenxv Jia / Jianwei Zeng / Mingxi Li / Ziyi Wang / Haixia Zhou / Linqi Zhang / Xinquan Wang / 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). | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_32959.map.gz | 6.8 MB | EMDB map data format | |
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Header (meta data) | emd-32959-v30.xml emd-32959.xml | 12.3 KB 12.3 KB | Display Display | EMDB header |
Images | emd_32959.png | 88 KB | ||
Filedesc metadata | emd-32959.cif.gz | 5.3 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-32959 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-32959 | HTTPS FTP |
-Validation report
Summary document | emd_32959_validation.pdf.gz | 318 KB | Display | EMDB validaton report |
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Full document | emd_32959_full_validation.pdf.gz | 317.5 KB | Display | |
Data in XML | emd_32959_validation.xml.gz | 6.4 KB | Display | |
Data in CIF | emd_32959_validation.cif.gz | 7.3 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-32959 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-32959 | HTTPS FTP |
-Related structure data
Related structure data | 7x26MC 7x25C 7x28C 7x29C 7x2aC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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-Map
File | Download / File: emd_32959.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.0825 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Sample components
-Entire : MERS-CoV Spike RBD domain with S41 Fab
Entire | Name: MERS-CoV Spike RBD domain with S41 Fab |
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Components |
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-Supramolecule #1: MERS-CoV Spike RBD domain with S41 Fab
Supramolecule | Name: MERS-CoV Spike RBD domain with S41 Fab / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
-Supramolecule #2: MERS-CoV Spike RBD domain
Supramolecule | Name: MERS-CoV Spike RBD domain / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #2 |
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Source (natural) | Organism: Homo sapiens (human) |
-Supramolecule #3: S41 Fab
Supramolecule | Name: S41 Fab / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #1, #3 |
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-Macromolecule #1: antibody S41 heavy chain
Macromolecule | Name: antibody S41 heavy chain / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 23.251098 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: QVQLVQSGAE VKKPGSSVKV SCKASGGTFS SYGITWVRQA PGQGLEWMGR IIPILGISRS VQKFQGRITI TADKSTSTAY MDLSGLTSD DTAVYYCARE GGSGYDFFDY WGQGTLVTVS SASTKGPSVF PLAPSSKSTS GGTAALGCLV KDYFPEPVTV S WNSGALTS ...String: QVQLVQSGAE VKKPGSSVKV SCKASGGTFS SYGITWVRQA PGQGLEWMGR IIPILGISRS VQKFQGRITI TADKSTSTAY MDLSGLTSD DTAVYYCARE GGSGYDFFDY WGQGTLVTVS SASTKGPSVF PLAPSSKSTS GGTAALGCLV KDYFPEPVTV S WNSGALTS GVHTFPAVLQ SSGLYSLSSV VTVPSSSLGT QTYICNVNHK PSNTKVDKRV EPK |
-Macromolecule #2: Spike glycoprotein
Macromolecule | Name: Spike glycoprotein / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
Molecular weight | Theoretical: 22.875826 KDa |
Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
Sequence | String: VECDFSPLLS GTPPQVYNFK RLVFTNCNYN LTKLLSLFSV NDFTCSQISP AAIASNCYSS LILDYFSYPL SMKSDLSVSS AGPISQFNY KQSFSNPTCL ILATVPHNLT TITKPLKYSY INKCSRLLSD DRTEVPQLVN ANQYSPCVST VPSTVWEDGD Y YRKQLSPL ...String: VECDFSPLLS GTPPQVYNFK RLVFTNCNYN LTKLLSLFSV NDFTCSQISP AAIASNCYSS LILDYFSYPL SMKSDLSVSS AGPISQFNY KQSFSNPTCL ILATVPHNLT TITKPLKYSY INKCSRLLSD DRTEVPQLVN ANQYSPCVST VPSTVWEDGD Y YRKQLSPL EGGGWLVASG STVAMTEQLQ MGFGITVQYG TDTNSVCPKA UniProtKB: Spike glycoprotein |
-Macromolecule #3: antibody S41 light chain
Macromolecule | Name: antibody S41 light chain / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 23.095535 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: EIVLTQSPGT LSLSPGERAT LSCRASQSVS SSYLAWYQQR PGQAPRLLIY GASSRATGIP DRFSGSGSGT DFTLTIGRLE PEDSAVYYC QQYGSSPWTF GQGTKVEIKR TVAAPSVFIF PPSDEQLKSG TASVVCLLNN FYPREAKVQW KVDNALQSGN S QESVTEQD ...String: EIVLTQSPGT LSLSPGERAT LSCRASQSVS SSYLAWYQQR PGQAPRLLIY GASSRATGIP DRFSGSGSGT DFTLTIGRLE PEDSAVYYC QQYGSSPWTF GQGTKVEIKR TVAAPSVFIF PPSDEQLKSG TASVVCLLNN FYPREAKVQW KVDNALQSGN S QESVTEQD SKDSTYSLSS TLTLSKADYE KHKVYACEVT HQGLSSPVTK SFNR |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.2 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: OTHER / Imaging mode: OTHER / Nominal defocus max: 3.0 µm / Nominal defocus min: 1.0 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: INSILICO MODEL |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.685 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 72778 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |