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Yorodumi- EMDB-23674: MERS-CoV S bound to the broadly neutralizing B6 Fab fragment (C3 ... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-23674 | |||||||||
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Title | MERS-CoV S bound to the broadly neutralizing B6 Fab fragment (C3 refinement) | |||||||||
Map data | Sharpened map | |||||||||
Sample |
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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 | Middle East respiratory syndrome-related coronavirus / Mus musculus (house mouse) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.5 Å | |||||||||
Authors | Sauer MM / Veesler D / Seattle Structural Genomics Center for Infectious Disease (SSGCID) | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Nat Struct Mol Biol / Year: 2021 Title: Structural basis for broad coronavirus neutralization. Authors: Maximilian M Sauer / M Alejandra Tortorici / Young-Jun Park / Alexandra C Walls / Leah Homad / Oliver J Acton / John E Bowen / Chunyan Wang / Xiaoli Xiong / Willem de van der Schueren / Joel ...Authors: Maximilian M Sauer / M Alejandra Tortorici / Young-Jun Park / Alexandra C Walls / Leah Homad / Oliver J Acton / John E Bowen / Chunyan Wang / Xiaoli Xiong / Willem de van der Schueren / Joel Quispe / Benjamin G Hoffstrom / Berend-Jan Bosch / Andrew T McGuire / David Veesler / Abstract: Three highly pathogenic β-coronaviruses have crossed the animal-to-human species barrier in the past two decades: SARS-CoV, MERS-CoV and SARS-CoV-2. To evaluate the possibility of identifying ...Three highly pathogenic β-coronaviruses have crossed the animal-to-human species barrier in the past two decades: SARS-CoV, MERS-CoV and SARS-CoV-2. To evaluate the possibility of identifying antibodies with broad neutralizing activity, we isolated a monoclonal antibody, termed B6, that cross-reacts with eight β-coronavirus spike glycoproteins, including all five human-infecting β-coronaviruses. B6 broadly neutralizes entry of pseudotyped viruses from lineages A and C, but not from lineage B, and the latter includes SARS-CoV and SARS-CoV-2. Cryo-EM, X-ray crystallography and membrane fusion assays reveal that B6 binds to a conserved cryptic epitope located in the fusion machinery. The data indicate that antibody binding sterically interferes with the spike conformational changes leading to membrane fusion. Our data provide a structural framework explaining B6 cross-reactivity with β-coronaviruses from three lineages, along with a proof of concept for antibody-mediated broad coronavirus neutralization elicited through vaccination. This study unveils an unexpected target for next-generation structure-guided design of a pan-β-coronavirus vaccine. | |||||||||
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_23674.map.gz | 230.3 MB | EMDB map data format | |
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Header (meta data) | emd-23674-v30.xml emd-23674.xml | 19.8 KB 19.8 KB | Display Display | EMDB header |
Images | emd_23674.png | 182 KB | ||
Others | emd_23674_additional_1.map.gz emd_23674_half_map_1.map.gz emd_23674_half_map_2.map.gz | 5.6 MB 226.9 MB 226.9 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-23674 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-23674 | HTTPS FTP |
-Validation report
Summary document | emd_23674_validation.pdf.gz | 829 KB | Display | EMDB validaton report |
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Full document | emd_23674_full_validation.pdf.gz | 828.6 KB | Display | |
Data in XML | emd_23674_validation.xml.gz | 15.7 KB | Display | |
Data in CIF | emd_23674_validation.cif.gz | 18.5 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-23674 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-23674 | HTTPS FTP |
-Related structure data
Related structure data | 7m5eMC 7m51C 7m52C 7m53C 7m55C 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_23674.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Sharpened map | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.05 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Additional map: Unsharpened map
File | emd_23674_additional_1.map | ||||||||||||
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Annotation | Unsharpened map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map A
File | emd_23674_half_map_1.map | ||||||||||||
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Annotation | Half map A | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map B
File | emd_23674_half_map_2.map | ||||||||||||
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Annotation | Half map B | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : MERS-CoV S ectodomain trimer bound to the B6 Fab fragment in the ...
Entire | Name: MERS-CoV S ectodomain trimer bound to the B6 Fab fragment in the presence of 100 mM neuraminic acid |
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Components |
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-Supramolecule #1: MERS-CoV S ectodomain trimer bound to the B6 Fab fragment in the ...
Supramolecule | Name: MERS-CoV S ectodomain trimer bound to the B6 Fab fragment in the presence of 100 mM neuraminic acid type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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-Supramolecule #2: MERS-CoV S ectodomain trimer
Supramolecule | Name: MERS-CoV S ectodomain trimer / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: Middle East respiratory syndrome-related coronavirus |
Recombinant expression | Organism: Homo sapiens (human) |
-Supramolecule #3: B6 Fab fragment
Supramolecule | Name: B6 Fab fragment / type: complex / ID: 3 / Parent: 1 |
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Source (natural) | Organism: Mus musculus (house mouse) |
Recombinant expression | Organism: Homo sapiens (human) |
-Macromolecule #1: Spike glycoprotein
Macromolecule | Name: Spike glycoprotein / 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: 149.172062 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MGILPSPGMP ALLSLVSLLS VLLMGCVAET GTVDVGPDSV KSACIEVDIQ QTFFDKTWPR PIDVSKADGI IYPQGRTYSN ITITYQGLF PYQGDHGDMY VYSAGHATGT TPQKLFVANY SQDVKQFANG FVVRIGAAAN STGTVIISPS TSATIRKIYP A FMLGSSVG ...String: MGILPSPGMP ALLSLVSLLS VLLMGCVAET GTVDVGPDSV KSACIEVDIQ QTFFDKTWPR PIDVSKADGI IYPQGRTYSN ITITYQGLF PYQGDHGDMY VYSAGHATGT TPQKLFVANY SQDVKQFANG FVVRIGAAAN STGTVIISPS TSATIRKIYP A FMLGSSVG NFSDGKMGRF FNHTLVLLPD GCGTLLRAFY CILEPRSGNH CPAGNSYTSF ATYHTPATDC SDGNYNRNAS LN SFKEYFN LRNCTFMYTY NITEDEILEW FGITQTAQGV HLFSSRYVDL YGGNMFQFAT LPVYDTIKYY SIIPHSIRSI QSD RKAWAA FYVYKLQPLT FLLDFSVDGY IRRAIDCGFN DLSQLHCSYE SFDVESGVYS VSSFEAKPSG SVVEQAEGVE CDFS PLLSG TPPQVYNFKR LVFTNCNYNL TKLLSLFSVN DFTCSQISPA AIASNCYSSL ILDYFSYPLS MKSDLSVSSA GPISQ FNYK QSFSNPTCLI LATVPHNLTT ITKPLKYSYI NKCSRLLSDD RTEVPQLVNA NQYSPCVSIV PSTVWEDGDY YRKQLS PLE GGGWLVASGS TVAMTEQLQM GFGITVQYGT DTNSVCPKLE FANDTKIASQ LGNCVEYSLY GVSGRGVFQN CTAVGVR QQ RFVYDAYQNL VGYYSDDGNY YCLRACVSVP VSVIYDKETK THATLFGSVA CEHISSTMSQ YSRSTRSMLK RRDSTYGP L QTPVGCVLGL VNSSLFVEDC KLPLGQSLCA LPDTPSTLTP ASVGSVPGEM RLASIAFNHP IQVDQLNSSY FKLSIPTNF SFGVTQEYIQ TTIQKVTVDC KQYVCNGFQK CEQLLREYGQ FCSKINQALH GANLRQDDSV RNLFASVKSS QSSPIIPGFG GDFNLTLLE PVSISTGSRS ARSAIEDLLF DKVTIADPGY MQGYDDCMQQ GPASARDLIC AQYVAGYKVL PPLMDVNMEA A YTSSLLGS IAGVGWTAGL SSFAAIPFAQ SIFYRLNGVG ITQQVLSENQ KLIANKFNQA LGAMQTGFTT TNEAFQKVQD AV NNNAQAL SKLASELSNT FGAISASIGD IIQRLDPPEQ DAQIDRLING RLTTLNAFVA QQLVRSESAA LSAQLAKDKV NEC VKAQSK RSGFCGQGTH IVSFVVNAPN GLYFMHVGYY PSNHIEVVSA YGLCDAANPT NCIAPVNGYF IKTNNTRIVD EWSY TGSSF YAPEPITSLN TKYVAPQVTY QNISTNLPPP LLGNSTGIDF QDELDEFFKN VSTSIPNFGS LTQINTTLLD LTYEM LSLQ QVVKALNESY IDLKELGNYT YYNKGSGREN LYFQGGGGSG YIPEAPRDGQ AYVRKDGEWV LLSTFLGHHH HHHHH |
-Macromolecule #7: FOLIC ACID
Macromolecule | Name: FOLIC ACID / type: ligand / ID: 7 / Number of copies: 3 / Formula: FOL |
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Molecular weight | Theoretical: 441.397 Da |
Chemical component information | ChemComp-FA: |
-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: 21 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ChemComp-NAG: |
-Macromolecule #9: N-acetyl-alpha-neuraminic acid
Macromolecule | Name: N-acetyl-alpha-neuraminic acid / type: ligand / ID: 9 / Number of copies: 3 / Formula: SIA |
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Molecular weight | Theoretical: 309.27 Da |
Chemical component information | ChemComp-SIA: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 8 |
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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 K2 SUMMIT (4k x 4k) / Average electron dose: 70.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: PDB ENTRY PDB model - PDB ID: |
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Final reconstruction | Applied symmetry - Point group: C3 (3 fold cyclic) / Resolution.type: BY AUTHOR / Resolution: 2.5 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 144792 |
Initial angle assignment | Type: PROJECTION MATCHING |
Final angle assignment | Type: PROJECTION MATCHING |