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Yorodumi- EMDB-14250: Structure of the SARS-CoV-2 spike glycoprotein in complex with th... -
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-Basic information
Entry | Database: EMDB / ID: EMD-14250 | ||||||||||||
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Title | Structure of the SARS-CoV-2 spike glycoprotein in complex with the 87G7 antibody Fab fragment | ||||||||||||
Map data | Composite map | ||||||||||||
Sample |
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Keywords | Coronavirus / Spike / Antibody / Complex / VIRAL PROTEIN | ||||||||||||
Function / homology | Function and homology information Maturation of spike protein / viral translation / Translation of Structural Proteins / Virion Assembly and Release / host cell surface / host extracellular space / suppression by virus of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion / host cell endoplasmic reticulum-Golgi intermediate compartment membrane ...Maturation of spike protein / viral translation / Translation of Structural Proteins / Virion Assembly and Release / host cell surface / host extracellular space / suppression by virus of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / entry receptor-mediated virion attachment to host cell / receptor-mediated endocytosis of virus by host cell / Attachment and Entry / membrane fusion / positive regulation of viral entry into host cell / receptor-mediated virion attachment to host cell / receptor ligand activity / host cell surface receptor binding / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / SARS-CoV-2 activates/modulates innate and adaptive immune responses / host cell plasma membrane / virion membrane / membrane / identical protein binding / plasma membrane Similarity search - Function | ||||||||||||
Biological species | Severe acute respiratory syndrome coronavirus 2 / Homo sapiens (human) | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.9 Å | ||||||||||||
Authors | Hurdiss DL / Drulyte I | ||||||||||||
Funding support | European Union, Germany, 3 items
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Citation | Journal: Sci Immunol / Year: 2022 Title: An ACE2-blocking antibody confers broad neutralization and protection against Omicron and other SARS-CoV-2 variants of concern. Authors: Wenjuan Du / Daniel L Hurdiss / Dubravka Drabek / Anna Z Mykytyn / Franziska K Kaiser / Mariana González-Hernández / Diego Muñoz-Santos / Mart M Lamers / Rien van Haperen / Wentao Li / ...Authors: Wenjuan Du / Daniel L Hurdiss / Dubravka Drabek / Anna Z Mykytyn / Franziska K Kaiser / Mariana González-Hernández / Diego Muñoz-Santos / Mart M Lamers / Rien van Haperen / Wentao Li / Ieva Drulyte / Chunyan Wang / Isabel Sola / Federico Armando / Georg Beythien / Malgorzata Ciurkiewicz / Wolfgang Baumgärtner / Kate Guilfoyle / Tony Smits / Joline van der Lee / Frank J M van Kuppeveld / Geert van Amerongen / Bart L Haagmans / Luis Enjuanes / Albert D M E Osterhaus / Frank Grosveld / Berend-Jan Bosch / Abstract: The ongoing evolution of SARS-CoV-2 has resulted in the emergence of Omicron, which displays notable immune escape potential through mutations at key antigenic sites on the spike protein. Many of ...The ongoing evolution of SARS-CoV-2 has resulted in the emergence of Omicron, which displays notable immune escape potential through mutations at key antigenic sites on the spike protein. Many of these mutations localize to the spike protein ACE2 receptor binding domain, annulling the neutralizing activity of therapeutic antibodies that were effective against other variants of concern (VOCs) earlier in the pandemic. Here, we identified a receptor-blocking human monoclonal antibody, 87G7, that retained potent in vitro neutralizing activity against SARS-CoV-2 variants including the Alpha, Beta, Gamma, Delta, and Omicron (BA.1/BA.2) VOCs. Using cryo-electron microscopy and site-directed mutagenesis experiments, we showed that 87G7 targets a patch of hydrophobic residues in the ACE2-binding site that are highly conserved in SARS-CoV-2 variants, explaining its broad neutralization capacity. 87G7 protected mice and hamsters prophylactically against challenge with all current SARS-CoV-2 VOCs and showed therapeutic activity against SARS-CoV-2 challenge in both animal models. Our findings demonstrate that 87G7 holds promise as a prophylactic or therapeutic agent for COVID-19 that is more resilient to SARS-CoV-2 antigenic diversity. | ||||||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_14250.map.gz | 92.3 MB | EMDB map data format | |
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Header (meta data) | emd-14250-v30.xml emd-14250.xml | 35.1 KB 35.1 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_14250_fsc.xml | 10.6 KB | Display | FSC data file |
Images | emd_14250.png | 96.6 KB | ||
Masks | emd_14250_msk_1.map | 103 MB | Mask map | |
Filedesc metadata | emd-14250.cif.gz | 8.2 KB | ||
Others | emd_14250_additional_1.map.gz emd_14250_additional_2.map.gz emd_14250_additional_3.map.gz emd_14250_additional_4.map.gz emd_14250_additional_5.map.gz emd_14250_half_map_1.map.gz emd_14250_half_map_2.map.gz | 1.6 MB 61.4 MB 91.9 MB 51.7 MB 97.3 MB 95.7 MB 95.7 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-14250 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-14250 | HTTPS FTP |
-Related structure data
Related structure data | 7r40MC 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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Related items in Molecule of the Month |
-Map
File | Download / File: emd_14250.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Annotation | Composite map | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.24 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_14250_msk_1.map | ||||||||||||
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Density Histograms |
-Additional map: Mask used for refinement
File | emd_14250_additional_1.map | ||||||||||||
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Annotation | Mask used for refinement | ||||||||||||
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Density Histograms |
-Additional map: Local resolution filtered map
File | emd_14250_additional_2.map | ||||||||||||
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Annotation | Local resolution filtered map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: DeepEMhancer sharpened map
File | emd_14250_additional_3.map | ||||||||||||
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Annotation | DeepEMhancer sharpened map | ||||||||||||
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-Additional map: Unsharpened map
File | emd_14250_additional_4.map | ||||||||||||
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Annotation | Unsharpened map | ||||||||||||
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Density Histograms |
-Additional map: Sharpened map
File | emd_14250_additional_5.map | ||||||||||||
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Annotation | Sharpened map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map 1
File | emd_14250_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_14250_half_map_2.map | ||||||||||||
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Annotation | Half map 2 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : SARS-CoV-2 spike glycoprotein in complex with the 87G7 antibody F...
Entire | Name: SARS-CoV-2 spike glycoprotein in complex with the 87G7 antibody Fab fragment |
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Components |
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-Supramolecule #1: SARS-CoV-2 spike glycoprotein in complex with the 87G7 antibody F...
Supramolecule | Name: SARS-CoV-2 spike glycoprotein in complex with the 87G7 antibody Fab fragment type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 |
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Molecular weight | Theoretical: 500 KDa |
-Supramolecule #2: SARS-CoV-2 spike glycoprotein
Supramolecule | Name: SARS-CoV-2 spike glycoprotein / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
-Supramolecule #3: 87G7 antibody Fab fragment
Supramolecule | Name: 87G7 antibody Fab fragment / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2-#3 |
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Source (natural) | 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: Severe acute respiratory syndrome coronavirus 2 |
Molecular weight | Theoretical: 141.048734 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: QCVNLTTRTQ LPPAYTNSFT RGVYYPDKVF RSSVLHSTQD LFLPFFSNVT WFHAIHVSGT NGTKRFDNPV LPFNDGVYFA STEKSNIIR GWIFGTTLDS KTQSLLIVNN ATNVVIKVCE FQFCNDPFLG VYYHKNNKSW MESEFRVYSS ANNCTFEYVS Q PFLMDLEG ...String: QCVNLTTRTQ LPPAYTNSFT RGVYYPDKVF RSSVLHSTQD LFLPFFSNVT WFHAIHVSGT NGTKRFDNPV LPFNDGVYFA STEKSNIIR GWIFGTTLDS KTQSLLIVNN ATNVVIKVCE FQFCNDPFLG VYYHKNNKSW MESEFRVYSS ANNCTFEYVS Q PFLMDLEG KQGNFKNLRE FVFKNIDGYF KIYSKHTPIN LVRDLPQGFS ALEPLVDLPI GINITRFQTL LALHRSYLTP GD SSSGWTA GAAAYYVGYL QPRTFLLKYN ENGTITDAVD CALDPLSETK CTLKSFTVEK GIYQTSNFRV QPTESIVRFP NIT NLCPFG EVFNATRFAS VYAWNRKRIS NCVADYSVLY NSASFSTFKC YGVSPTKLND LCFTNVYADS FVIRGDEVRQ IAPG QTGKI ADYNYKLPDD FTGCVIAWNS NNLDSKVGGN YNYLYRLFRK SNLKPFERDI STEIYQAGST PCNGVEGFNC YFPLQ SYGF QPTNGVGYQP YRVVVLSFEL LHAPATVCGP KKSTNLVKNK CVNFNFNGLT GTGVLTESNK KFLPFQQFGR DIADTT DAV RDPQTLEILD ITPCSFGGVS VITPGTNTSN QVAVLYQDVN CTEVPVAIHA DQLTPTWRVY STGSNVFQTR AGCLIGA EH VNNSYECDIP IGAGICASYQ TQTNSPAAAR SVASQSIIAY TMSLGAENSV AYSNNSIAIP TNFTISVTTE ILPVSMTK T SVDCTMYICG DSTECSNLLL QYGSFCTQLN RALTGIAVEQ DKNTQEVFAQ VKQIYKTPPI KDFGGFNFSQ ILPDPSKPS KRSPIEDLLF NKVTLADAGF IKQYGDCLGD IAARDLICAQ KFNGLTVLPP LLTDEMIAQY TSALLAGTIT SGWTFGAGPA LQIPFPMQM AYRFNGIGVT QNVLYENQKL IANQFNSAIG KIQDSLSSTP SALGKLQDVV NQNAQALNTL VKQLSSNFGA I SSVLNDIL SRLDPPEAEV QIDRLITGRL QSLQTYVTQQ LIRAAEIRAS ANLAATKMSE CVLGQSKRVD FCGKGYHLMS FP QSAPHGV VFLHVTYVPA QEKNFTTAPA ICHDGKAHFP REGVFVSNGT HWFVTQRNFY EPQIITTDNT FVSGNCDVVI GIV NNTVYD PLQPELDSFK EELDKYFKNH TSPDVDLGDI SGINASVVNI QKEIDRLNEV AKNLNESLID LQELGKYEQG SGYI PEAPR DGQAYVRKDG EWVLLSTFLG RSLEVLFQGP GHHHHHHHHS AWSHPQFEKG GGSGGGGSGG SAWSHPQFEK UniProtKB: Spike glycoprotein |
-Macromolecule #2: 87G7 light chain variable region
Macromolecule | Name: 87G7 light chain variable region / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 23.550207 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: EIVLTQSPAT LSLSPGERAT LSCRASQSFH NYLAWYQQKP GRAPRLLIFD ASNRATGIPA RFSGSGSGTD FTLTISSLEP EDFAVYYCQ QRFNWPLTFG GGTKVEIKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS Q ESVTEQDS ...String: EIVLTQSPAT LSLSPGERAT LSCRASQSFH NYLAWYQQKP GRAPRLLIFD ASNRATGIPA RFSGSGSGTD FTLTISSLEP EDFAVYYCQ QRFNWPLTFG GGTKVEIKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS Q ESVTEQDS KDSTYSLSST LTLSKADYEK HKVYACEVTH QGLSSPVTKS FNRGEC |
-Macromolecule #3: 87G7 heavy chain variable region
Macromolecule | Name: 87G7 heavy chain variable region / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 23.915703 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: EVQLLESGGG LVQPGGSLRL SCVASGFTFS SYVMSWVRQA PGKGLEWVAA ISGSGGNTYY ADSVKGRFTI SRDNSKNTLY LQMNSLRAE DTAVYYCAKE GTYYYGSGSF WGQGTLVTVS SASTKGPSVF PLAPSSKSTS GGTAALGCLV KDYFPEPVTV S WNSGALTS ...String: EVQLLESGGG LVQPGGSLRL SCVASGFTFS SYVMSWVRQA PGKGLEWVAA ISGSGGNTYY ADSVKGRFTI SRDNSKNTLY LQMNSLRAE DTAVYYCAKE GTYYYGSGSF WGQGTLVTVS SASTKGPSVF PLAPSSKSTS GGTAALGCLV KDYFPEPVTV S WNSGALTS GVHTFPAVLQ SSGLYSLSSV VTVPSSSLGT QTYICNVNHK PSNTKVDKKV EPKSCDKTH |
-Macromolecule #5: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 5 / Number of copies: 27 / 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
Concentration | 4 mg/mL |
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Buffer | pH: 8 |
Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER |
Vitrification | Cryogen name: ETHANE / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | TFS KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | C2 aperture diameter: 70.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Cs: 2.7 mm / Nominal defocus max: 1.5 µm / Nominal defocus min: 0.5 µm / Nominal magnification: 130000 |
Specialist optics | Energy filter - Name: TFS Selectris X / Energy filter - Slit width: 10 eV |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Digitization - Dimensions - Width: 4096 pixel / Digitization - Dimensions - Height: 4096 pixel / Number grids imaged: 2 / Number real images: 3831 / Average electron dose: 51.5 e/Å2 Details: 1331 images collected from grid 1 (0.02% FOM) and 2500 images collected from grid 2 (0% FOM) |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
-Atomic model buiding 1
Initial model |
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Output model | PDB-7r40: |