+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-24403 | |||||||||
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Title | SARS-CoV-2 Spike in complex with PVI.V6-14 Fab | |||||||||
Map data | Sharpened map of the full spike in complex with PVI.V6-14 Fab | |||||||||
Sample |
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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 / entry receptor-mediated virion attachment to host cell ...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 / entry receptor-mediated virion attachment to host cell / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / membrane fusion / receptor-mediated endocytosis of virus by host cell / Attachment and Entry / positive regulation of viral entry into host cell / receptor-mediated virion attachment to host cell / receptor ligand activity / symbiont-mediated suppression of host innate immune response / 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 / identical protein binding / membrane / plasma membrane Similarity search - Function | |||||||||
Biological species | Severe acute respiratory syndrome coronavirus 2 / Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.6 Å | |||||||||
Authors | Altomare CG / Bajic G | |||||||||
Funding support | United States, 2 items
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Citation | Journal: mBio / Year: 2022 Title: Structure of a Vaccine-Induced, Germline-Encoded Human Antibody Defines a Neutralizing Epitope on the SARS-CoV-2 Spike N-Terminal Domain. Authors: Clara G Altomare / Daniel C Adelsberg / Juan Manuel Carreno / Iden A Sapse / Fatima Amanat / Ali H Ellebedy / Viviana Simon / Florian Krammer / Goran Bajic / Abstract: Structural characterization of infection- and vaccination-elicited antibodies in complex with antigen provides insight into the evolutionary arms race between the host and the pathogen and informs ...Structural characterization of infection- and vaccination-elicited antibodies in complex with antigen provides insight into the evolutionary arms race between the host and the pathogen and informs rational vaccine immunogen design. We isolated a germ line-encoded monoclonal antibody (mAb) from plasmablasts activated upon mRNA vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and determined its structure in complex with the spike glycoprotein by electron cryomicroscopy (cryo-EM). We show that the mAb engages a previously uncharacterized neutralizing epitope on the spike N-terminal domain (NTD). The high-resolution structure reveals details of the intermolecular interactions and shows that the mAb inserts its heavy complementarity-determining region 3 (HCDR3) loop into a hydrophobic NTD cavity previously shown to bind a heme metabolite, biliverdin. We demonstrate direct competition with biliverdin and that, because of the conserved nature of the epitope, the mAb maintains binding to viral variants B.1.1.7 (alpha), B.1.351 (beta), B.1.617.2 (delta), and B.1.1.529 (omicron). Our study describes a novel conserved epitope on the NTD that is readily targeted by vaccine-induced antibody responses. We report the first structure of a vaccine-induced antibody to SARS-CoV-2 spike isolated from plasmablasts 7 days after vaccination. The genetic sequence of the antibody PVI.V6-14 suggests that it is completely unmutated, meaning that this type of B cell did not undergo somatic hypermutation or affinity maturation; this cell was likely already present in the donor and was activated by the vaccine. This is, to our knowledge, also the first structure of an unmutated antibody in complex with its cognate antigen. PVI.V6-14 binds a novel, conserved epitope on the N-terminal domain (NTD) and neutralizes the original viral strain. PVI.V6-14 also binds the newly emerged variants B.1.1.7 (alpha), B.1.351 (beta), B.1.617.2 (delta), and B.1.1.529 (omicron). Given that this antibody was likely already present in the donor prior to vaccination, we believe that this antibody class could potentially "keep up" with the new variants, should they continue to emerge, by undergoing somatic hypermutation and affinity maturation. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_24403.map.gz | 981 MB | EMDB map data format | |
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Header (meta data) | emd-24403-v30.xml emd-24403.xml | 16.5 KB 16.5 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_24403_fsc.xml | 21.6 KB | Display | FSC data file |
Images | emd_24403.png | 33.1 KB | ||
Others | emd_24403_additional_1.map.gz | 512.1 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-24403 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-24403 | HTTPS FTP |
-Validation report
Summary document | emd_24403_validation.pdf.gz | 479.3 KB | Display | EMDB validaton report |
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Full document | emd_24403_full_validation.pdf.gz | 478.9 KB | Display | |
Data in XML | emd_24403_validation.xml.gz | 19 KB | Display | |
Data in CIF | emd_24403_validation.cif.gz | 26.4 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-24403 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-24403 | HTTPS FTP |
-Related structure data
Related structure data | 7rbvMC 7rbuC C: citing same article (ref.) M: atomic model generated by this map |
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Similar structure data | Similarity search - Function & homologyF&H Search |
EM raw data | EMPIAR-11127 (Title: Structure of a Vaccine-Induced, Germline-Encoded Human Antibody Defines a Neutralizing Epitope on the SARS-CoV-2 Spike N-Terminal Domain Data size: 5.1 TB Data #1: Unaligned multi-frame movies of SARS-CoV-2 spike glycoprotein in complex with PVI.V6-14 Fab [micrographs - multiframe]) |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_24403.map.gz / Format: CCP4 / Size: 1 GB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Annotation | Sharpened map of the full spike in complex with PVI.V6-14 Fab | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.56 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Additional map: Unsharpened map of the full spike in complex with PVI.V6-14 Fab
File | emd_24403_additional_1.map | ||||||||||||
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Annotation | Unsharpened map of the full spike in complex with PVI.V6-14 Fab | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : SARS-CoV-2 Spike:PVI.V6-14 Fab complex
Entire | Name: SARS-CoV-2 Spike:PVI.V6-14 Fab complex |
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Components |
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-Supramolecule #1: SARS-CoV-2 Spike:PVI.V6-14 Fab complex
Supramolecule | Name: SARS-CoV-2 Spike:PVI.V6-14 Fab complex / type: complex / Chimera: Yes / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
Molecular weight | Theoretical: 550 KDa |
-Macromolecule #1: PVI.V6-14 Fab light chain, variable region
Macromolecule | Name: PVI.V6-14 Fab light chain, variable region / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 11.385669 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: DIQMTQSPSS VSASVGDRVT ITCRASQGIS SWLAWYQQKP GKAPKLLIYA ASSLQSGVPS RFSGSGSGTD FTLTISSLQP EDFATYYCQ QANSFPLTFG GGTKVEIK |
-Macromolecule #2: PVI.V6-14 Fab heavy chain, variable region
Macromolecule | Name: PVI.V6-14 Fab heavy chain, variable region / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 13.932396 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: QVQLQESGPG LVKPSETLSL TCTVSGGSIS SSSYYWGWIR QPPGKGLEWI GSIYYSGSTY YNPSLKSRVT ISVDTSKNQF SLKLSSVTA ADTAVYYCAR CRPEYYFGSG SYLDFDYWGQ GTLVTVSS |
-Macromolecule #3: Spike glycoprotein
Macromolecule | Name: Spike glycoprotein / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
Molecular weight | Theoretical: 136.448016 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 TQTNSPGSAS 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 RSLEVLF |
-Macromolecule #9: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 9 / 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
Concentration | 1 mg/mL |
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Buffer | pH: 7.5 |
Grid | Model: Quantifoil R0.6/1 / Material: GOLD / Mesh: 400 / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Atmosphere: AIR |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (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: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 0.8 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |