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Yorodumi- EMDB-19017: S1B domain of the PDCoV spike glycoprotein in complex with the 67... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-19017 | |||||||||
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Title | S1B domain of the PDCoV spike glycoprotein in complex with the 67B12 and 46E6 antibody Fab fragments | |||||||||
Map data | ||||||||||
Sample |
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Keywords | Spike / coronavirus / antibody / complex / RBD / S1B / VIRAL PROTEIN | |||||||||
Function / homology | Function and homology information endocytosis involved in viral entry into host cell / 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 / virion membrane / membrane Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Porcine deltacoronavirus | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.9 Å | |||||||||
Authors | Debski-Antoniak O / Drulyte I / Hurdiss DL | |||||||||
Funding support | Switzerland, 1 items
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Citation | Journal: Nat Commun / Year: 2024 Title: Neutralizing antibodies reveal cryptic vulnerabilities and interdomain crosstalk in the porcine deltacoronavirus spike protein. Authors: Wenjuan Du / Oliver Debski-Antoniak / Dubravka Drabek / Rien van Haperen / Melissa van Dortmondt / Joline van der Lee / Ieva Drulyte / Frank J M van Kuppeveld / Frank Grosveld / Daniel L ...Authors: Wenjuan Du / Oliver Debski-Antoniak / Dubravka Drabek / Rien van Haperen / Melissa van Dortmondt / Joline van der Lee / Ieva Drulyte / Frank J M van Kuppeveld / Frank Grosveld / Daniel L Hurdiss / Berend-Jan Bosch / Abstract: Porcine deltacoronavirus (PDCoV) is an emerging enteric pathogen that has recently been detected in humans. Despite this zoonotic concern, the antigenic structure of PDCoV remains unknown. The virus ...Porcine deltacoronavirus (PDCoV) is an emerging enteric pathogen that has recently been detected in humans. Despite this zoonotic concern, the antigenic structure of PDCoV remains unknown. The virus relies on its spike (S) protein for cell entry, making it a prime target for neutralizing antibodies. Here, we generate and characterize a set of neutralizing antibodies targeting the S protein, shedding light on PDCoV S interdomain crosstalk and its vulnerable sites. Among the four identified antibodies, one targets the S1A domain, causing local and long-range conformational changes, resulting in partial exposure of the S1B domain. The other antibodies bind the S1B domain, disrupting binding to aminopeptidase N (APN), the entry receptor for PDCoV. Notably, the epitopes of these S1B-targeting antibodies are concealed in the prefusion S trimer conformation, highlighting the necessity for conformational changes for effective antibody binding. The binding footprint of one S1B binder entirely overlaps with APN-interacting residues and thus targets a highly conserved epitope. These findings provide structural insights into the humoral immune response against the PDCoV S protein, potentially guiding vaccine and therapeutic development for this zoonotic pathogen. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_19017.map.gz | 52 MB | EMDB map data format | |
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Header (meta data) | emd-19017-v30.xml emd-19017.xml | 20.6 KB 20.6 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_19017_fsc.xml | 9.9 KB | Display | FSC data file |
Images | emd_19017.png | 23.8 KB | ||
Masks | emd_19017_msk_1.map | 103 MB | Mask map | |
Filedesc metadata | emd-19017.cif.gz | 6.6 KB | ||
Others | emd_19017_half_map_1.map.gz emd_19017_half_map_2.map.gz | 95.6 MB 95.6 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-19017 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-19017 | HTTPS FTP |
-Validation report
Summary document | emd_19017_validation.pdf.gz | 878.6 KB | Display | EMDB validaton report |
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Full document | emd_19017_full_validation.pdf.gz | 878.1 KB | Display | |
Data in XML | emd_19017_validation.xml.gz | 18.3 KB | Display | |
Data in CIF | emd_19017_validation.cif.gz | 23.7 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-19017 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-19017 | HTTPS FTP |
-Related structure data
Related structure data | 8r9zMC 8r9wC 8r9xC 8r9yC 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_19017.map.gz / Format: CCP4 / Size: 103 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: 0.97333 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_19017_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_19017_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_19017_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : PDCoV spike S1B domain in complex with the 67B12 and 46E6 antibod...
Entire | Name: PDCoV spike S1B domain in complex with the 67B12 and 46E6 antibody Fab fragments |
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Components |
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-Supramolecule #1: PDCoV spike S1B domain in complex with the 67B12 and 46E6 antibod...
Supramolecule | Name: PDCoV spike S1B domain in complex with the 67B12 and 46E6 antibody Fab fragments type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#5 |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 105.24 KDa |
-Macromolecule #1: Spike protein
Macromolecule | Name: Spike protein / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Porcine deltacoronavirus |
Molecular weight | Theoretical: 12.787479 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: LEVVQLNISA HMDFGEARLD SVTINGNTSY CVTKPYFRLE TNFMCTGCTM NLRTDTCSFD LSAVNNGMSF SQFCLSTESG ACEMKIIVT YVWNYLLRQR LYVTAVEGQT HTGTT UniProtKB: Spike protein |
-Macromolecule #2: 67B12 antibody heavy chain
Macromolecule | Name: 67B12 antibody heavy chain / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 22.964826 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: VQLVQSGAEV KKPGSSVKVS CKASGGTFSS LAISWVRQAP GQGLEWMGGI IPTFGTTNYA QNFRGRVTIT ADKSTSTAYM ELSTLISED TAVYFCARER STDTWPGDAF DIWGQGTMVT VSSASTKGPS VFPLAPSSGT AALGCLVKDY FPEPVTVSWN S GALTSGVH ...String: VQLVQSGAEV KKPGSSVKVS CKASGGTFSS LAISWVRQAP GQGLEWMGGI IPTFGTTNYA QNFRGRVTIT ADKSTSTAYM ELSTLISED TAVYFCARER STDTWPGDAF DIWGQGTMVT VSSASTKGPS VFPLAPSSGT AALGCLVKDY FPEPVTVSWN S GALTSGVH TFPAVLQSSG LYSLSSVVTV PSSSLLGQTY ICNVNHKPSN TKVDKKVEPK |
-Macromolecule #3: 67B12 antibody light chain
Macromolecule | Name: 67B12 antibody 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: 23.037592 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: EILMTQSPAT LSVSPGERAT LSCWASQSVN SKLAWYQQKP GQAPRLLIYD TSTRATGIPA RFSGSGSGAE FTLTISSLQS EDFAVYYCQ QYNYWPYTFG QGTKLEIKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS Q ESVTEQDS ...String: EILMTQSPAT LSVSPGERAT LSCWASQSVN SKLAWYQQKP GQAPRLLIYD TSTRATGIPA RFSGSGSGAE FTLTISSLQS EDFAVYYCQ QYNYWPYTFG QGTKLEIKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS Q ESVTEQDS KDSTYSLSST LTLSKADYEK HKVYACEVTH QGLSSPVTKS F |
-Macromolecule #4: 46E6 antibody heavy chain
Macromolecule | Name: 46E6 antibody heavy chain / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 23.508619 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: QVQLVESGGG VVQPGRSLRL SCAASGFTFS SYAMHWVRQA PGKGLEWVAV IWRDGSNEFY ADSVKGRFTI SRDNSKDTLY LQMNSLRAE DTAVYYCARR GIIMVRGLLG YWGQGTLVTV SSASTKGPSV FPLAPSSKSG TAALGCLVKD YFPEPVTVSW N SGALTSGV ...String: QVQLVESGGG VVQPGRSLRL SCAASGFTFS SYAMHWVRQA PGKGLEWVAV IWRDGSNEFY ADSVKGRFTI SRDNSKDTLY LQMNSLRAE DTAVYYCARR GIIMVRGLLG YWGQGTLVTV SSASTKGPSV FPLAPSSKSG TAALGCLVKD YFPEPVTVSW N SGALTSGV HTFPAVLQSS GLYSLSSVVT VPSSSLGTQT YICNVNHKPS NTKVDKKVEP K |
-Macromolecule #5: 46E6 antibody heavy chain
Macromolecule | Name: 46E6 antibody heavy chain / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 23.017627 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: DIQMTQSPPS LSASVGDRVT ITCRASQGIS NYLAWHQQKP GKVPKLLIYT ASTLQSGVPS RFSGSGSGTD FTLTISSLQP EDVATYYCQ KYNSAPFTFG PGTKVDIKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS Q ESVTEQDS ...String: DIQMTQSPPS LSASVGDRVT ITCRASQGIS NYLAWHQQKP GKVPKLLIYT ASTLQSGVPS RFSGSGSGTD FTLTISSLQP EDVATYYCQ KYNSAPFTFG PGTKVDIKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS Q ESVTEQDS KDSTYSLSST LTLSKADYEK HKVYACEVTH QGLSSPVTKS FNRG |
-Macromolecule #7: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 7 / Number of copies: 1 / 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: 7.8 |
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Vitrification | Cryogen name: ETHANE / Chamber humidity: 90 % / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | TFS KRIOS |
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Specialist optics | Energy filter - Name: TFS Selectris |
Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.5 µm / Nominal defocus min: 0.75 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
+Image processing
-Atomic model buiding 1
Initial model | PDB ID: Chain - Chain ID: A / Chain - Source name: PDB / Chain - Initial model type: experimental model |
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Details | Initial fitting was done using Chimera |
Refinement | Space: REAL / Protocol: RIGID BODY FIT / Target criteria: Cross-correlation coefficient |
Output model | PDB-8r9z: |