+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-20527 | |||||||||
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Title | MERS S0 trimer in complex with antibody G2 | |||||||||
Map data | MERS S0 trimer in complex with variable domain of antibody G2 | |||||||||
Sample |
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Function / homology | Function and homology information : / membrane => GO:0016020 / 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 => GO:0016020 / 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 / metal ion binding Similarity search - Function | |||||||||
Biological species | Middle East respiratory syndrome-related coronavirus / Mus musculus (house mouse) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.19 Å | |||||||||
Authors | Bowman CA / Pallesen J / Ward AB | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Cell Rep / Year: 2019 Title: Structural Definition of a Neutralization-Sensitive Epitope on the MERS-CoV S1-NTD. Authors: Nianshuang Wang / Osnat Rosen / Lingshu Wang / Hannah L Turner / Laura J Stevens / Kizzmekia S Corbett / Charles A Bowman / Jesper Pallesen / Wei Shi / Yi Zhang / Kwanyee Leung / Robert N ...Authors: Nianshuang Wang / Osnat Rosen / Lingshu Wang / Hannah L Turner / Laura J Stevens / Kizzmekia S Corbett / Charles A Bowman / Jesper Pallesen / Wei Shi / Yi Zhang / Kwanyee Leung / Robert N Kirchdoerfer / Michelle M Becker / Mark R Denison / James D Chappell / Andrew B Ward / Barney S Graham / Jason S McLellan / Abstract: Middle East respiratory syndrome coronavirus (MERS-CoV) emerged into the human population in 2012 and has caused substantial morbidity and mortality. Potently neutralizing antibodies targeting the ...Middle East respiratory syndrome coronavirus (MERS-CoV) emerged into the human population in 2012 and has caused substantial morbidity and mortality. Potently neutralizing antibodies targeting the receptor-binding domain (RBD) on MERS-CoV spike (S) protein have been characterized, but much less is known about antibodies targeting non-RBD epitopes. Here, we report the structural and functional characterization of G2, a neutralizing antibody targeting the MERS-CoV S1 N-terminal domain (S1-NTD). Structures of G2 alone and in complex with the MERS-CoV S1-NTD define a site of vulnerability comprising two loops, each of which contain a residue mutated in G2-escape variants. Cell-surface binding studies and in vitro competition experiments demonstrate that G2 strongly disrupts the attachment of MERS-CoV S to its receptor, dipeptidyl peptidase-4 (DPP4), with the inhibition requiring the native trimeric S conformation. These results advance our understanding of antibody-mediated neutralization of coronaviruses and should facilitate the development of immunotherapeutics and vaccines against MERS-CoV. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_20527.map.gz | 154.4 MB | EMDB map data format | |
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Header (meta data) | emd-20527-v30.xml emd-20527.xml | 22 KB 22 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_20527_fsc.xml | 12.7 KB | Display | FSC data file |
Images | emd_20527.png | 119.6 KB | ||
Masks | emd_20527_msk_1.map | 163.6 MB | Mask map | |
Others | emd_20527_half_map_1.map.gz emd_20527_half_map_2.map.gz | 151.6 MB 151.6 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-20527 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-20527 | HTTPS FTP |
-Validation report
Summary document | emd_20527_validation.pdf.gz | 1 MB | Display | EMDB validaton report |
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Full document | emd_20527_full_validation.pdf.gz | 1 MB | Display | |
Data in XML | emd_20527_validation.xml.gz | 20.2 KB | Display | |
Data in CIF | emd_20527_validation.cif.gz | 26 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-20527 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-20527 | HTTPS FTP |
-Related structure data
Related structure data | 6pz8MC 0486C 6pxgC 6pxhC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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-Map
File | Download / File: emd_20527.map.gz / Format: CCP4 / Size: 163.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | MERS S0 trimer in complex with variable domain of antibody G2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.02 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Mask #1
File | emd_20527_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: Half Map #1
File | emd_20527_half_map_1.map | ||||||||||||
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Annotation | Half Map #1 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half Map #2
File | emd_20527_half_map_2.map | ||||||||||||
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Annotation | Half Map #2 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : MERS S0 ectodomain trimer in complex with antibody G2
Entire | Name: MERS S0 ectodomain trimer in complex with antibody G2 |
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Components |
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-Supramolecule #1: MERS S0 ectodomain trimer in complex with antibody G2
Supramolecule | Name: MERS S0 ectodomain trimer in complex with antibody G2 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4 |
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-Supramolecule #2: MERS S0 ectodomain trimer
Supramolecule | Name: MERS S0 ectodomain trimer / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: Middle East respiratory syndrome-related coronavirus |
Recombinant expression | Organism: Homo sapiens (human) |
-Supramolecule #3: antibody G2
Supramolecule | Name: antibody G2 / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #3-#4 |
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Source (natural) | Organism: Mus musculus (house mouse) |
Recombinant expression | Organism: Homo sapiens (human) |
-Macromolecule #1: S protein
Macromolecule | Name: S protein / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Middle East respiratory syndrome-related coronavirus |
Molecular weight | Theoretical: 51.301617 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: SVPGEMRLAS IAFNHPIQVD QLNSSYFKLS IPTNFSFGVT QEYIQTTIQK VTVDCKQYVC NGFQKCEQLL REYGQFCSKI NQALHGANL RQDDSVRNLF ASVKSSQSSP IIPGFGGDFN LTLLEPVSIS TGSRSARSAI EDLLFDKVTI ADPGYMQGYD D CMQQGPAS ...String: SVPGEMRLAS IAFNHPIQVD QLNSSYFKLS IPTNFSFGVT QEYIQTTIQK VTVDCKQYVC NGFQKCEQLL REYGQFCSKI NQALHGANL RQDDSVRNLF ASVKSSQSSP IIPGFGGDFN LTLLEPVSIS TGSRSARSAI EDLLFDKVTI ADPGYMQGYD D CMQQGPAS ARDLICAQYV AGYKVLPPLM DVNMEAAYTS SLLGSIAGVG WTAGLSSFAA IPFAQSIFYR LNGVGITQQV LS ENQKLIA NKFNQALGAM QTGFTTTNEA FHKVQDAVNN NAQALSKLAS ELSNTFGAIS ASIGDIIQRL DVLEQDAQID RLI NGRLTT LNAFVAQQLV RSESAALSAQ LAKDKVNECV KAQSKRSGFC GQGTHIVSFV VNAPNGLYFM HVGYYPSNHI EVVS AYGLC DAANPTNCIA PVNGYFIKTN NTRIVDEWSY TGSSFYAPEP ITSLNTKYVA PQVTYQNIST NLPPPLL |
-Macromolecule #2: S protein
Macromolecule | Name: S protein / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Middle East respiratory syndrome-related coronavirus |
Molecular weight | Theoretical: 80.409109 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: YVDVGPDSVK SACIEVDIQQ TFFDKTWPRP IDVSKADGII YPQGRTYSNI TITYQGLFPY QGDHGDMYVY SAGHATGTTP QKLFVANYS QDVKQFANGF VVRIGAAANS TGTVIISPST SATIRKIYPA FMLGSSVGNF SDGKMGRFFN HTLVLLPDGC G TLLRAFYC ...String: YVDVGPDSVK SACIEVDIQQ TFFDKTWPRP IDVSKADGII YPQGRTYSNI TITYQGLFPY QGDHGDMYVY SAGHATGTTP QKLFVANYS QDVKQFANGF VVRIGAAANS TGTVIISPST SATIRKIYPA FMLGSSVGNF SDGKMGRFFN HTLVLLPDGC G TLLRAFYC ILEPRSGNHC PAGNSYTSFA TYHTPATDCS DGNYNRNASL NSFKEYFNLR NCTFMYTYNI TEDEILEWFG IT QTAQGVH LFSSRYVDLY GGNMFQFATL PVYDTIKYYS IIPHSIRSIQ SDRKAWAAFY VYKLQPLTFL LDFSVDGYIR RAI DCGFND LSQLHCSYES FDVESGVYSV SSFEAKPSGS VVEQAEGVEC DFSPLLSGTP PQVYNFKRLV FTNCNYNLTK LLSL FSVND FTCSQISPAA IASNCYSSLI LDYFSYPLSM KSDLSVSSAG PISQFNYKQS FSNPTCLILA TVPHNLTTIT KPLKY SYIN KCSRLLSDDR TEVPQLVNAN QYSPCVSIVP STVWEDGDYY RKQLSPLEGG GWLVASGSTV AMTEQLQMGF GITVQY GTD TNSVCPKLEF ANDTKIASQL GNCVEYSLYG VSGRGVFQNC TAVGVRQQRF VYDAYQNLVG YYSDDGNYYC LRACVSV PV SVIYDKETKT HATLFGSVAC EHISSTMSQY SRSTRSMLKR RDSTYGPLQT PVGCVLGLVN SSLFVEDCKL PLGQSLCA L PDTPS |
-Macromolecule #3: G2 heavy chain
Macromolecule | Name: G2 heavy chain / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 24.275059 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: QVQLQQSGGE LVKPGASVKL SCKTSGFTFS SSYISWLKQK PGQSLEWIAW IYAGTGGTEY NQKFTGKAQV TVDTSSSTAY MQFSSLTTE DSAIYYCARG GSSFAMDYWG QGTSVTVSSA STTPPSVYPL APGSAAQTNS MVTLGCLVKG YFPEPVTVTW N SGSLSSGV ...String: QVQLQQSGGE LVKPGASVKL SCKTSGFTFS SSYISWLKQK PGQSLEWIAW IYAGTGGTEY NQKFTGKAQV TVDTSSSTAY MQFSSLTTE DSAIYYCARG GSSFAMDYWG QGTSVTVSSA STTPPSVYPL APGSAAQTNS MVTLGCLVKG YFPEPVTVTW N SGSLSSGV HTFPAVLQSD LYTLSSSVTV PSSTWPSETV TCNVAHPASS TKVDKKIVPR DCGKGLEVLF Q |
-Macromolecule #4: G2 light chain
Macromolecule | Name: G2 light chain / type: protein_or_peptide / ID: 4 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 23.861293 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: QLVLTQSPAS LAVSLGQRAT ISCRASESVD NYGISFMNWF QQKPGQPPKL LIHTASNQGS GVPARFSGSG SGTDFSLNIH PVEDDDTAM YFCQQSEEVP LTFGAGTKLE IKRTDAAPTV SIFPPSSEQL TSGGASVVCF LNNFYPKDIN VKWKIDGSER Q NGVLNSWT ...String: QLVLTQSPAS LAVSLGQRAT ISCRASESVD NYGISFMNWF QQKPGQPPKL LIHTASNQGS GVPARFSGSG SGTDFSLNIH PVEDDDTAM YFCQQSEEVP LTFGAGTKLE IKRTDAAPTV SIFPPSSEQL TSGGASVVCF LNNFYPKDIN VKWKIDGSER Q NGVLNSWT DQDSKDSTYS MSSTLTLTKD EYERHNSYTC EATHKTSTSP IVKSFNRNEC |
-Macromolecule #8: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 8 / Number of copies: 18 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ChemComp-NAG: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
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Grid | Details: unspecified |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: SUPER-RESOLUTION / Average electron dose: 77.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: SPOT SCAN / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |