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- EMDB-75194: SARS-CoV-2 spike S2 subunit in complex with polyclonal Fabs (Apex... -

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Basic information

Entry
Database: EMDB / ID: EMD-75194
TitleSARS-CoV-2 spike S2 subunit in complex with polyclonal Fabs (Apex-B epitope)
Map data3D map of the SARS-CoV-2 spike S2 subunit with polyclonal antibodies from donor2 bound to the S2 Apex-B epitope, determined by ns-EMPEM.
Sample
  • Complex: SARS-CoV-2 S2 subunit in complex with polyclonal Fabs (Apex-A epitope)
KeywordsSARS-CoV-2 / Coronavirus / Immune system / antibody / VIRAL PROTEIN / VIRAL PROTEIN-Immune System complex
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / negative staining / Resolution: 24.0 Å
AuthorsPark S / Ward AB
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)P01 AI172531 United States
CitationJournal: bioRxiv / Year: 2026
Title: The buried S2 apex of SARS-CoV-2 spike elicits an immunodominant germline-restricted public antibody response.
Authors: Suncheol Park / Jacob Mischka / Nisreen Okba / Anass Abbad / Meng Yuan / Komal Srivastava / Charles Gleason / Lubbertus C F Mulder / Jeffrey Copps / Katrina Saam / Sandhya Bangaru / Florian ...Authors: Suncheol Park / Jacob Mischka / Nisreen Okba / Anass Abbad / Meng Yuan / Komal Srivastava / Charles Gleason / Lubbertus C F Mulder / Jeffrey Copps / Katrina Saam / Sandhya Bangaru / Florian Krammer / Ian A Wilson / Viviana Simon / Andrew B Ward
Abstract: The continued mutational pressure on the SARS-CoV-2 S1 subunit underscores the need to target the conserved S2 region for pan-coronavirus vaccine development. A detailed molecular understanding of S2- ...The continued mutational pressure on the SARS-CoV-2 S1 subunit underscores the need to target the conserved S2 region for pan-coronavirus vaccine development. A detailed molecular understanding of S2-directed immune responses is therefore essential. In this study, we identified the S2 apex as the most immunodominant epitope within the S2 subunit, eliciting robust antibody responses despite occlusion by S1, using electron-microscopy-based polyclonal epitope mapping (EMPEM) of plasma from infected and vaccinated individuals. Structure-guided sequence analysis with antibody databases revealed that antibodies targeting a poorly characterized S2 Apex-B site form a convergent public clonotype, which is predominantly derived from the IGHV3-30 germline with a 14-residue CDRH3 containing a G/S-G-S/N-Y motif. This clonotype is extensively expanded, accounting for up to 40% of total spike-reactive antibody sequence counts in individual vaccinated donors. This study elucidates the molecular basis the high-frequency elicitation of this non-neutralizing clonotype emphasizing that its immunodominance acts as a primary hurdle for universal coronavirus vaccines and underscore the need for precision antigen design to redirect immunity toward more potent neutralizing targets.
History
DepositionJan 21, 2026-
Header (metadata) releaseMar 11, 2026-
Map releaseMar 11, 2026-
UpdateMar 11, 2026-
Current statusMar 11, 2026Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

Downloads & links

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Map

FileDownload / File: emd_75194.map.gz / Format: CCP4 / Size: 27 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Annotation3D map of the SARS-CoV-2 spike S2 subunit with polyclonal antibodies from donor2 bound to the S2 Apex-B epitope, determined by ns-EMPEM.
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
2 Å/pix.
x 192 pix.
= 384. Å
2 Å/pix.
x 192 pix.
= 384. Å
2 Å/pix.
x 192 pix.
= 384. Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 2 Å
Density
Contour LevelBy AUTHOR: 0.03
Minimum - Maximum-0.03315887 - 0.09235571
Average (Standard dev.)0.000018019295 (±0.0037154972)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions192192192
Spacing192192192
CellA=B=C: 384.0 Å
α=β=γ: 90.0 °

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Supplemental data

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Additional map: 3D map of the SARS-CoV-2 spike S2 subunit...

Fileemd_75194_additional_1.map
Annotation3D map of the SARS-CoV-2 spike S2 subunit with polyclonal antibodies from donor3 bound to the S2 Apex-B epitope, determined by ns-EMPEM.
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Additional map: 3D map of the SARS-CoV-2 spike S2 subunit...

Fileemd_75194_additional_10.map
Annotation3D map of the SARS-CoV-2 spike S2 subunit with polyclonal antibodies from donor8-T3 bound to the S2 Apex-B epitope, determined by ns-EMPEM.
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Additional map: 3D map of the SARS-CoV-2 spike S2 subunit...

Fileemd_75194_additional_11.map
Annotation3D map of the SARS-CoV-2 spike S2 subunit with polyclonal antibodies from donor9-T2 bound to the S2 Apex-B epitope, determined by ns-EMPEM.
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Additional map: 3D map of the SARS-CoV-2 spike S2 subunit...

Fileemd_75194_additional_12.map
Annotation3D map of the SARS-CoV-2 spike S2 subunit with polyclonal antibodies from donor9-T1 bound to the S2 Apex-B epitope, determined by ns-EMPEM.
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Additional map: 3D map of the SARS-CoV-2 spike S2 subunit...

Fileemd_75194_additional_2.map
Annotation3D map of the SARS-CoV-2 spike S2 subunit with polyclonal antibodies from donor6 bound to the S2 Apex-B epitope, determined by ns-EMPEM.
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Additional map: 3D map of the SARS-CoV-2 spike S2 subunit...

Fileemd_75194_additional_3.map
Annotation3D map of the SARS-CoV-2 spike S2 subunit with polyclonal antibodies from donor7 bound to the S2 Apex-B epitope, determined by ns-EMPEM.
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Additional map: 3D map of the SARS-CoV-2 spike S2 subunit...

Fileemd_75194_additional_4.map
Annotation3D map of the SARS-CoV-2 spike S2 subunit with polyclonal antibodies from donor4 bound to the S2 Apex-B epitope, determined by ns-EMPEM.
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Additional map: 3D map of the SARS-CoV-2 spike S2 subunit...

Fileemd_75194_additional_5.map
Annotation3D map of the SARS-CoV-2 spike S2 subunit with polyclonal antibodies from donor5 bound to the S2 Apex-B epitope, determined by ns-EMPEM.
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Additional map: 3D map of the SARS-CoV-2 spike S2 subunit...

Fileemd_75194_additional_6.map
Annotation3D map of the SARS-CoV-2 spike S2 subunit with polyclonal antibodies from donor1 bound to the S2 Apex-B epitope, determined by ns-EMPEM.
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Additional map: 3D map of the SARS-CoV-2 spike S2 subunit...

Fileemd_75194_additional_7.map
Annotation3D map of the SARS-CoV-2 spike S2 subunit with polyclonal antibodies from donor8-T1 bound to the S2 Apex-B epitope, determined by ns-EMPEM.
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

+
Additional map: 3D map of the SARS-CoV-2 spike S2 subunit...

Fileemd_75194_additional_8.map
Annotation3D map of the SARS-CoV-2 spike S2 subunit with polyclonal antibodies from donor8-T2 bound to the S2 Apex-B epitope, determined by ns-EMPEM.
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

+
Additional map: 3D map of the SARS-CoV-2 spike S2 subunit...

Fileemd_75194_additional_9.map
Annotation3D map of the SARS-CoV-2 spike S2 subunit with polyclonal antibodies from donor8-T2 bound to the S2 Apex-B epitope, determined by ns-EMPEM.
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Half map: Half Map B

Fileemd_75194_half_map_1.map
AnnotationHalf Map B
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Half map: Half Map A

Fileemd_75194_half_map_2.map
AnnotationHalf Map A
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Sample components

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Entire : SARS-CoV-2 S2 subunit in complex with polyclonal Fabs (Apex-A epitope)

EntireName: SARS-CoV-2 S2 subunit in complex with polyclonal Fabs (Apex-A epitope)
Components
  • Complex: SARS-CoV-2 S2 subunit in complex with polyclonal Fabs (Apex-A epitope)

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Supramolecule #1: SARS-CoV-2 S2 subunit in complex with polyclonal Fabs (Apex-A epitope)

SupramoleculeName: SARS-CoV-2 S2 subunit in complex with polyclonal Fabs (Apex-A epitope)
type: complex / ID: 1 / Parent: 0
Source (natural)Organism: Homo sapiens (human)

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Experimental details

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Structure determination

Methodnegative staining
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

Concentration0.01 mg/mL
BufferpH: 7.5
StainingType: NEGATIVE / Material: Uranyl Formate

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Electron microscopy

MicroscopeTFS TALOS F200C
Image recordingFilm or detector model: FEI CETA (4k x 4k) / Average electron dose: 27.1 e/Å2
Electron beamAcceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 2.0 µm
Sample stageCooling holder cryogen: NITROGEN
Experimental equipment
Model: Tecnai F20 / Image courtesy: FEI Company

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Image processing

CTF correctionType: NONE
Startup modelType of model: EMDB MAP
EMDB ID:
Final reconstructionApplied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 24.0 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION (ver. 4.0) / Number images used: 12853
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

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