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Open data
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Basic information
| Entry | Database: PDB / ID: 9z18 | |||||||||||||||||||||||||||
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| Title | SARS-CoV-2 spike S2 in complex with antibody N6-2 | |||||||||||||||||||||||||||
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Keywords | VIRAL PROTEIN / SARS-CoV-2 spike / antibody / viral glycoprotein | |||||||||||||||||||||||||||
| Function / homology | Function and homology informationsymbiont-mediated disruption of host tissue / Maturation of spike protein / host cell surface / Translation of Structural Proteins / Virion Assembly and Release / Lectin pathway of complement activation / host extracellular region / symbiont-mediated-mediated suppression of host tetherin activity / structural constituent of virion / Induction of Cell-Cell Fusion ...symbiont-mediated disruption of host tissue / Maturation of spike protein / host cell surface / Translation of Structural Proteins / Virion Assembly and Release / Lectin pathway of complement activation / host extracellular region / symbiont-mediated-mediated suppression of host tetherin activity / structural constituent of virion / Induction of Cell-Cell Fusion / positive regulation of viral entry into host cell / Initial triggering of complement / membrane fusion / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / Attachment and Entry / entry receptor-mediated virion attachment to host cell / receptor-mediated virion attachment to host cell / host cell surface receptor binding / symbiont-mediated suppression of host innate immune response / endocytosis involved in viral entry into host cell / receptor ligand activity / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / symbiont entry into host cell / virion attachment to host cell / host cell plasma membrane / SARS-CoV-2 activates/modulates innate and adaptive immune responses / virion membrane / membrane / identical protein binding / plasma membrane Similarity search - Function | |||||||||||||||||||||||||||
| Biological species | Homo sapiens (human)![]() | |||||||||||||||||||||||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.9 Å | |||||||||||||||||||||||||||
Authors | Zhou, L. / Hsieh, C. / McLellan, J.S. | |||||||||||||||||||||||||||
| Funding support | 1items
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Citation | Journal: PLoS Pathog / Year: 2026Title: Structural and functional characterization of a conserved cryptic epitope on SARS-CoV-2 spike S2 subunit. Authors: Ling Zhou / Ching-Lin Hsieh / Sarah R Leist / Emily Happy Miller / Andrew P Horton / Sophie R Shoemaker / Elizabeth C Gardner / John M Powers / Daniel R Boutz / Michael L Mallory / Connor M ...Authors: Ling Zhou / Ching-Lin Hsieh / Sarah R Leist / Emily Happy Miller / Andrew P Horton / Sophie R Shoemaker / Elizabeth C Gardner / John M Powers / Daniel R Boutz / Michael L Mallory / Connor M Mullins / Nicole V Johnson / Alexandra L Tse / Albert Wang / Kamyab Javanmardi / Lily E Adams / Jonathan Schisler / Susan Marqusee / Kartik Chandran / Ralph S Baric / Jimmy D Gollihar / Jason S McLellan / ![]() Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has undergone extensive evolution since its emergence in 2019, underscoring the continuous need for vaccines and therapeutics effective ...Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has undergone extensive evolution since its emergence in 2019, underscoring the continuous need for vaccines and therapeutics effective against multiple variants of concern (VOCs). The S2 subunit of the viral spike (S) glycoprotein is highly conserved among sarbecoviruses, making it an attractive target for broadly protective countermeasures. To elucidate the S2 antigenic landscape, we employed yeast surface display to isolate S2-targeted antibodies from COVID-19 convalescent donors. Biophysical characterization revealed that these S2 apex-directed antibodies preferentially bind to open spike conformations and a stabilized S2 construct but not to the closed, trimeric prefusion spike. Cryo-electron microscopy structures defined a cryptic epitope encompassing the upper helix and fusion peptide proximal region on S2. This epitope is conserved among sarbecoviruses but remains largely occluded in the closed prefusion conformation of the spikes. As a result, the antibodies exhibited weak neutralization activity against SARS-CoV-2 pseudoviruses, failed to neutralize authentic viruses, and did not provide protection in a lethal mouse challenge model using a mouse-adapted SARS-CoV-2 strain. These findings highlight a non-neutralizing epitope on S2 capable of eliciting antibodies during SARS-CoV-2 infection in humans and provide valuable reagents for probing S2 conformational dynamics and optimizing S2-based vaccine antigens. | |||||||||||||||||||||||||||
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Structure visualization
| Structure viewer | Molecule: Molmil Jmol/JSmol |
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Downloads & links
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Download
| PDBx/mmCIF format | 9z18.cif.gz | 128 KB | Display | PDBx/mmCIF format |
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| PDB format | pdb9z18.ent.gz | 94.3 KB | Display | PDB format |
| PDBx/mmJSON format | 9z18.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/z1/9z18 ftp://data.pdbj.org/pub/pdb/validation_reports/z1/9z18 | HTTPS FTP |
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-Related structure data
| Related structure data | ![]() 73732MC ![]() 9z12C M: map data used to model this data C: citing same article ( |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
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Assembly
| Deposited unit | ![]()
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Components
| #1: Antibody | Mass: 13481.926 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) |
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| #2: Antibody | Mass: 13508.205 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) |
| #3: Protein | Mass: 56151.293 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() Gene: S, 2 / Production host: Homo sapiens (human) / References: UniProt: P0DTC2 |
| #4: Sugar | ChemComp-NAG / |
| Has ligand of interest | N |
| Has protein modification | Y |
-Experimental details
-Experiment
| Experiment | Method: ELECTRON MICROSCOPY |
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| EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
| Component | Name: SARS-CoV-2 spike S2 in complex with antibody N6-2 / Type: COMPLEX / Entity ID: #1-#3 / Source: RECOMBINANT |
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| Source (natural) | Organism: Homo sapiens (human) |
| Source (recombinant) | Organism: Homo sapiens (human) |
| Buffer solution | pH: 7.5 |
| Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
| Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
| Microscopy | Model: TFS GLACIOS |
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| Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: FLOOD BEAM |
| Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2500 nm / Nominal defocus min: 1000 nm |
| Image recording | Electron dose: 40 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) |
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Processing
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| CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||
| 3D reconstruction | Resolution: 2.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 1797906 / Symmetry type: POINT |
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Homo sapiens (human)

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FIELD EMISSION GUN