+Open data
-Basic information
Entry | Database: PDB / ID: 7rbu | |||||||||
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Title | SARS-CoV-2 Spike in complex with PVI.V6-14 Fab | |||||||||
Components |
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Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / virus / neutralizing antibody / vaccine / plasmablast / VIRAL PROTEIN-IMMUNE SYSTEM complex | |||||||||
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 / receptor-mediated endocytosis of virus by host cell / membrane fusion / Attachment and Entry / 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 / identical protein binding / membrane / plasma membrane Similarity search - Function | |||||||||
Biological species | Severe acute respiratory syndrome coronavirus 2 Homo sapiens (human) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.7 Å | |||||||||
Authors | Altomare, C.G. / Bajic, G. | |||||||||
Funding support | United States, 2items
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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
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7rbu.cif.gz | 101.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7rbu.ent.gz | 79.2 KB | Display | PDB format |
PDBx/mmJSON format | 7rbu.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7rbu_validation.pdf.gz | 814.7 KB | Display | wwPDB validaton report |
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Full document | 7rbu_full_validation.pdf.gz | 820.2 KB | Display | |
Data in XML | 7rbu_validation.xml.gz | 34.9 KB | Display | |
Data in CIF | 7rbu_validation.cif.gz | 50.5 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/rb/7rbu ftp://data.pdbj.org/pub/pdb/validation_reports/rb/7rbu | HTTPS FTP |
-Related structure data
Related structure data | 24402MC 7rbvC M: map data used to model this data C: citing same article (ref.) |
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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
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 33417.703 Da / Num. of mol.: 1 / Fragment: N-terminal domain (UNP residues 14-307) Source method: isolated from a genetically manipulated source Source: (gene. exp.) Severe acute respiratory syndrome coronavirus 2 Gene: S, 2 / Cell line (production host): Expi293 / Production host: Homo sapiens (human) / References: UniProt: P0DTC2 | ||||
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#2: Antibody | Mass: 13932.396 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): Expi293 / Production host: Homo sapiens (human) | ||||
#3: Antibody | Mass: 11385.669 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell (production host): Expi293 / Cell line (production host): Expi293 / Production host: Homo sapiens (human) / References: UniProt: A0A5C2FYK4 | ||||
#4: Polysaccharide | Source method: isolated from a genetically manipulated source #5: Sugar | Has ligand of interest | N | |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: SARS-CoV-2 Spike:PVI.V6-14 Fab complex / Type: COMPLEX / Entity ID: #1-#3 / Source: MULTIPLE SOURCES |
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Molecular weight | Value: 550 kDa/nm / Experimental value: NO |
Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
Source (recombinant) | Organism: Homo sapiens (human) / Cell: Expi293 |
Buffer solution | pH: 7.5 |
Specimen | Conc.: 1 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2500 nm / Nominal defocus min: 800 nm |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.19.2_4158: / Classification: refinement | ||||||||||||||||||||||||
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EM software | Name: RELION / Version: 3.1.2 / Category: 3D reconstruction | ||||||||||||||||||||||||
CTF correction | Type: NONE | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.7 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 60639 / Symmetry type: POINT | ||||||||||||||||||||||||
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