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- EMDB-74739: SARS-CoV-2 S2 in complex with COV2-2509 -

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Basic information

Entry
Database: EMDB / ID: EMD-74739
TitleSARS-CoV-2 S2 in complex with COV2-2509
Map dataSARS-CoV-2 S2 in complex with COV2-2509
Sample
  • Complex: SARS-CoV-2 S2 in complex with COV2-2509
    • Protein or peptide: COV2-2509 Fab-Heavy chain
    • Protein or peptide: COV2-2509 Fab-Light chain
    • Protein or peptide: Spike protein S2
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
KeywordsSARS-CoV-2 / Coronavirus / Immune system / antibody / VIRAL PROTEIN / VIRAL PROTEIN-Immune System complex
Function / homology
Function and homology information


symbiont-mediated disruption of host tissue / Maturation of spike protein / Translation of Structural Proteins / Virion Assembly and Release / host cell surface / host extracellular space / symbiont-mediated-mediated suppression of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion / membrane fusion ...symbiont-mediated disruption of host tissue / Maturation of spike protein / Translation of Structural Proteins / Virion Assembly and Release / host cell surface / host extracellular space / symbiont-mediated-mediated suppression of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion / membrane fusion / Attachment and Entry / entry receptor-mediated virion attachment to host cell / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / positive regulation of viral entry into 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
Spike (S) protein S1 subunit, receptor-binding domain, SARS-CoV-2 / Spike (S) protein S1 subunit, N-terminal domain, SARS-CoV-like / Coronavirus spike glycoprotein S1, C-terminal / Coronavirus spike glycoprotein S1, C-terminal / Spike glycoprotein, N-terminal domain superfamily / Spike S1 subunit, receptor binding domain superfamily, betacoronavirus / Spike glycoprotein, betacoronavirus / Betacoronavirus spike (S) glycoprotein S1 subunit N-terminal (NTD) domain profile. / Spike glycoprotein S1, N-terminal domain, betacoronavirus-like / Betacoronavirus-like spike glycoprotein S1, N-terminal ...Spike (S) protein S1 subunit, receptor-binding domain, SARS-CoV-2 / Spike (S) protein S1 subunit, N-terminal domain, SARS-CoV-like / Coronavirus spike glycoprotein S1, C-terminal / Coronavirus spike glycoprotein S1, C-terminal / Spike glycoprotein, N-terminal domain superfamily / Spike S1 subunit, receptor binding domain superfamily, betacoronavirus / Spike glycoprotein, betacoronavirus / Betacoronavirus spike (S) glycoprotein S1 subunit N-terminal (NTD) domain profile. / Spike glycoprotein S1, N-terminal domain, betacoronavirus-like / Betacoronavirus-like spike glycoprotein S1, N-terminal / Betacoronavirus spike (S) glycoprotein S1 subunit C-terminal (CTD) domain profile. / Spike (S) protein S1 subunit, receptor-binding domain, betacoronavirus / Betacoronavirus spike glycoprotein S1, receptor binding / Spike glycoprotein S2 superfamily, coronavirus / Spike glycoprotein S2, coronavirus, heptad repeat 1 / Spike glycoprotein S2, coronavirus, heptad repeat 2 / Coronavirus spike (S) glycoprotein S2 subunit heptad repeat 1 (HR1) region profile. / Coronavirus spike (S) glycoprotein S2 subunit heptad repeat 2 (HR2) region profile. / Spike glycoprotein S2, coronavirus / Coronavirus spike glycoprotein S2
Similarity search - Domain/homology
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.11 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
DepositionDec 23, 2025-
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

emd_74739.png

Downloads & links

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Map

FileDownload / File: emd_74739.map.gz / Format: CCP4 / Size: 476.8 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationSARS-CoV-2 S2 in complex with COV2-2509
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.72 Å/pix.
x 500 pix.
= 359. Å		0.72 Å/pix.
x 500 pix.
= 359. Å		0.72 Å/pix.
x 500 pix.
= 359. Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.718 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.07
Minimum - Maximum-0.5105254 - 0.76250094
Average (Standard dev.)-0.000006950218 (±0.015047567)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions500500500
Spacing500500500
CellA=B=C: 359.0 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_74739_msk_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: Half Map B

Fileemd_74739_half_map_1.map
AnnotationHalf Map B
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: Half Map A

Fileemd_74739_half_map_2.map
AnnotationHalf Map A
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : SARS-CoV-2 S2 in complex with COV2-2509

EntireName: SARS-CoV-2 S2 in complex with COV2-2509
Components
  • Complex: SARS-CoV-2 S2 in complex with COV2-2509
    • Protein or peptide: COV2-2509 Fab-Heavy chain
    • Protein or peptide: COV2-2509 Fab-Light chain
    • Protein or peptide: Spike protein S2
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose

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Supramolecule #1: SARS-CoV-2 S2 in complex with COV2-2509

SupramoleculeName: SARS-CoV-2 S2 in complex with COV2-2509 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: COV2-2509 Fab-Heavy chain

MacromoleculeName: COV2-2509 Fab-Heavy chain / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 23.965881 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: QVQLVESGGG VVQPGRSLRL SCAASGFIFS TYAMHWVRQA PGKGLEWVAV ISYDGDNKYY ADSVKGRFTI SRDNSKNTLY LEMNSLRAE DTAVYYCARP RGGSYQTCFD YWGQGTLVTV SSASTKGPSV FPLAPSSKST SGGTAALGCL VKDYFPEPVT V SWNSGALT ...String:
QVQLVESGGG VVQPGRSLRL SCAASGFIFS TYAMHWVRQA PGKGLEWVAV ISYDGDNKYY ADSVKGRFTI SRDNSKNTLY LEMNSLRAE DTAVYYCARP RGGSYQTCFD YWGQGTLVTV SSASTKGPSV FPLAPSSKST SGGTAALGCL VKDYFPEPVT V SWNSGALT SGVHTFPAVL QSSGLYSLSS VVTVPSSSLG TQTYICNVNH KPSNTKVDKK VEPKSC

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Macromolecule #2: COV2-2509 Fab-Light chain

MacromoleculeName: COV2-2509 Fab-Light chain / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 23.285793 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: EIVMTQSPAT LSVSPGERAT LSCRASQSVS SNLAWYQQKP GQAPRLLIYG ASTRATGIPA RFSGSGSGTE FTLTISSLQS EDFAVYYCQ QYNNWPGTFG QGTKVEIKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS Q ESVTEQDS ...String:
EIVMTQSPAT LSVSPGERAT LSCRASQSVS SNLAWYQQKP GQAPRLLIYG ASTRATGIPA RFSGSGSGTE FTLTISSLQS EDFAVYYCQ QYNNWPGTFG QGTKVEIKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS Q ESVTEQDS KDSTYSLSST LTLSKADYEK HKVYACEVTH QGLSSPVTKS FNRGEC

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Macromolecule #3: Spike protein S2

MacromoleculeName: Spike protein S2 / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 52.342074 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: SLGAENCVAY SNNSIAIPTN FTISVTTEIL PVSMTKTSVD CTMYICGDST ECSNLLLQYG SFCTQLNRAL TGIAVEQDKN TQEVFAQVK QIYCTPPIKD FGGFNFSQIL PDPSKPSKRS FIEDLLFNKV TLADAGFIKQ YGDCLGDIAA RDLICAQKFN G LTVLPPLL ...String:
SLGAENCVAY SNNSIAIPTN FTISVTTEIL PVSMTKTSVD CTMYICGDST ECSNLLLQYG SFCTQLNRAL TGIAVEQDKN TQEVFAQVK QIYCTPPIKD FGGFNFSQIL PDPSKPSKRS FIEDLLFNKV TLADAGFIKQ YGDCLGDIAA RDLICAQKFN G LTVLPPLL TDEMIAQYTS ALLACTITSG WTCGAGPALQ IPFPMQMAYR FNGIGVTQNV LYENQKLIAN QFNSAIGKIQ DS LSSTPSA LGKLQDVVNQ NAQALNFLVK QLSSNFGAIS SVLNDILSRL DPPEAEWQID RLIWGRLQSL QTYVTQQLIR AAE IRASAN LAATKMSECV LGQSKRVDFC GKGYHLMSFP QSAPHGVVFL HVTYVPAQEK NFTTAPAICH DGKAHFPREG VFVS NGTHW FVTQRNFYEP QIITTDNTFV SGNCDVVIGI VNNTVYDPLQ PELDSFKEEL DKYFKNHTSG SHHHHHHHH

UniProtKB: Spike glycoprotein

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Macromolecule #5: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 5 / Number of copies: 4 / Formula: NAG
Molecular weightTheoretical: 221.208 Da
Chemical component information

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

Concentration0.5 mg/mL
BufferpH: 7.5
Component:
ConcentrationFormulaName
20.0 mMTrisTris
150.0 mMNaClSodium Chloride
GridModel: UltrAuFoil R1.2/1.3 / Material: GOLD / Mesh: 300 / Support film - Material: GOLD / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV

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Electron microscopy

MicroscopeTFS GLACIOS
Image recordingFilm or detector model: TFS FALCON 4i (4k x 4k) / Average electron dose: 45.0 e/Å2
Electron beamAcceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 1.8 µm / Nominal defocus min: 0.8 µm / Nominal magnification: 190000
Sample stageSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN

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Image processing

CTF correctionSoftware - Name: cryoSPARC / Type: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: INSILICO MODEL / In silico model: ab initio reconstruction
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.11 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 139283
Initial angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC
Final angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC
Final 3D classificationSoftware - Name: cryoSPARC
FSC plot (resolution estimation)

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Atomic model buiding 1

Initial modelPDB ID:

6xr8


Chain - Source name: PDB / Chain - Initial model type: experimental model
RefinementSpace: REAL
Output model

PDB-9zt7:
SARS-CoV-2 S2 in complex with COV2-2509

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