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- EMDB-67630: Cryo-EM map of SARS-CoV-2 spike complexed with Fab 12C2 -

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Basic information

Entry
Database: EMDB / ID: EMD-67630
TitleCryo-EM map of SARS-CoV-2 spike complexed with Fab 12C2
Map data
Sample
  • Complex: SARS-CoV-2 spike complexed with Fab 12C2
    • Other: SARS-CoV-2 spike protein
    • Other: Fab 12C2 Heavy Chain
    • Other: Fab 12C2 Light Chain
KeywordsSARS-CoV-2 spike protein / Antibodies / VIRAL PROTEIN-IMMUNE SYSTEM complex / VIRAL PROTEIN
Biological speciesSevere acute respiratory syndrome coronavirus 2
Methodsingle particle reconstruction / cryo EM / Resolution: 3.02 Å
AuthorsDeng Z / Zhao H / Yu F
Funding support1 items
OrganizationGrant numberCountry
Not funded
CitationJournal: Viruses / Year: 2025
Title: Broadly Sarbecovirus-Neutralizing Antibodies Induced by Ancestral SARS-CoV-2 Infection.
Authors: Yiwei Zhang / Zhen Zhang / Feiyang Yu / Xianying Chen / Shangyu Yang / Jingyi Lin / Genmao Liu / Xinyang Liu / Ming Guo / Yu Chen / Ke Lan / Haiyan Zhao /
Abstract: The COVID-19 pandemic, driven by SARS-CoV-2, continues to challenge global health due to emerging variants and the potential risk posed by related sarbecoviruses. Neutralizing antibodies targeting ...The COVID-19 pandemic, driven by SARS-CoV-2, continues to challenge global health due to emerging variants and the potential risk posed by related sarbecoviruses. Neutralizing antibodies targeting the spike (S) glycoprotein, particularly the receptor-binding domain (RBD), play a crucial role in viral neutralization and vaccine design. Although broadly neutralizing anti-RBD antibodies have been identified, the nature of cross-reactive humoral responses induced by natural infection with ancestral SARS-CoV-2 strains remains incompletely understood. Here, we isolated 105 S-specific monoclonal antibodies (mAbs) from individuals recovered from prototype SARS-CoV-2 infection. Of these, 30 mAbs cross-recognized SARS-CoV-1, including 25 RBD-directed mAbs, of which 12 displayed cross-neutralizing activity against both viruses. Among them, mAb 12C2 potently neutralized SARS-CoV-1 and multiple SARS-CoV-2 variants, likely through mechanisms that include inhibition of membrane fusion and potential destabilization of the S trimer. Cryo-electron microscopy revealed that 12C2 engages the outer face of the RBD, overlapping with the epitope recognized by the broadly neutralizing antibody S309 derived from SARS-CoV-1 convalescent. Collectively, these findings demonstrate that ancestral SARS-CoV-2 infection can elicit robust cross-neutralizing antibody responses and provide valuable insights for the design of broadly protective antibodies and vaccines.
History
DepositionDec 11, 2025-
Header (metadata) releaseJan 21, 2026-
Map releaseJan 21, 2026-
UpdateJan 21, 2026-
Current statusJan 21, 2026Processing site: PDBc / Status: Released

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Structure visualization

Supplemental images

emd_67630.png

Downloads & links

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Map

FileDownload / File: emd_67630.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.95 Å/pix.
x 320 pix.
= 304. Å		0.95 Å/pix.
x 320 pix.
= 304. Å		0.95 Å/pix.
x 320 pix.
= 304. Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.95 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.143
Minimum - Maximum-1.2192868 - 2.0578597
Average (Standard dev.)-0.000050238003 (±0.034313895)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions320320320
Spacing320320320
CellA=B=C: 304.0 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #1

Fileemd_67630_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #2

Fileemd_67630_half_map_2.map
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 spike complexed with Fab 12C2

EntireName: SARS-CoV-2 spike complexed with Fab 12C2
Components
  • Complex: SARS-CoV-2 spike complexed with Fab 12C2
    • Other: SARS-CoV-2 spike protein
    • Other: Fab 12C2 Heavy Chain
    • Other: Fab 12C2 Light Chain

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Supramolecule #1: SARS-CoV-2 spike complexed with Fab 12C2

SupramoleculeName: SARS-CoV-2 spike complexed with Fab 12C2 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Severe acute respiratory syndrome coronavirus 2

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Macromolecule #1: SARS-CoV-2 spike protein

MacromoleculeName: SARS-CoV-2 spike protein / type: other / ID: 1 / Classification: other
Source (natural)Organism: Severe acute respiratory syndrome coronavirus 2
SequenceString: QCVNLTTRTQ LPPAYTNSFT RGVYYPDKVF RSSVLHSTQD LFLPFFSNVT WFHAIHVSGT NGTKRFDNPV LPFNDGVYFA STEKSNIIRG WIFGTTLDSK TQSLLIVNNA TNVVIKVCEF QFCNDPFLGV YYHKNNKSWM ESEFRVYSSA NNCTFEYVSQ PFLMDLEGKQ ...String:
QCVNLTTRTQ LPPAYTNSFT RGVYYPDKVF RSSVLHSTQD LFLPFFSNVT WFHAIHVSGT NGTKRFDNPV LPFNDGVYFA STEKSNIIRG WIFGTTLDSK TQSLLIVNNA TNVVIKVCEF QFCNDPFLGV YYHKNNKSWM ESEFRVYSSA NNCTFEYVSQ PFLMDLEGKQ GNFKNLREFV FKNIDGYFKI YSKHTPINLV RDLPQGFSAL EPLVDLPIGI NITRFQTLLA LHRSYLTPGD SSSGWTAGAA AYYVGYLQPR TFLLKYNENG TITDAVDCAL DPLSETKCTL KSFTVEKGIY QTSNFRVQPT ESIVRFPNIT NLCPFGEVFN ATRFASVYAW NRKRISNCVA DYSVLYNSAS FSTFKCYGVS PTKLNDLCFT NVYADSFVIR GDEVRQIAPG QTGKIADYNY KLPDDFTGCV IAWNSNNLDS KVGGNYNYLY RLFRKSNLKP FERDISTEIY QAGSTPCNGV EGFNCYFPLQ SYGFQPTNGV GYQPYRVVVL SFELLHAPAT VCGPKKSTNL VKNKCVNFNF NGLTGTGVLT ESNKKFLPFQ QFGRDIADTT DAVRDPQTLE ILDITPCSFG GVSVITPGTN TSNQVAVLYQ DVNCTEVPVA IHADQLTPTW RVYSTGSNVF QTRAGCLIGA EHVNNSYECD IPIGAGICAS YQTQTNSPAS VASQSIIAYT MSLGAENSVA YSNNSIAIPT NFTISVTTEI LPVSMTKTSV DCTMYICGDS TECSNLLLQY GSFCTQLNRA LTGIAVEQDK NTQEVFAQVK QIYKTPPIKD FGGFNFSQIL PDPSKPSKRS PIEDLLFNKV TLADAGFIKQ YGDCLGDIAA RDLICAQKFN GLTVLPPLLT DEMIAQYTSA LLAGTITSGW TFGAGPALQI PFPMQMAYRF NGIGVTQNVL YENQKLIANQ FNSAIGKIQD SLSSTPSALG KLQDVVNQNA QALNTLVKQL SSNFGAISSV LNDILSRLDP PEAEVQIDRL ITGRLQSLQT YVTQQLIRAA EIRASANLAA TKMSECVLGQ SKRVDFCGKG YHLMSFPQSA PHGVVFLHVT YVPAQEKNFT TAPAICHDGK AHFPREGVFV SNGTHWFVTQ RNFYEPQIIT TDNTFVSGNC DVVIGIVNNT VYDPLQPELD SFKEELDKYF KNHTSPDVDL GDISGINASV VNIQKEIDRL NEVAKNLNES LIDLQELGKY EQYIKWPSGR LVPRGSPGSG YIPEAPRDGQ AYVRKDGEWV LLSTFLGHHH HHH
Recombinant expressionOrganism: Homo sapiens (human)

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Macromolecule #2: Fab 12C2 Heavy Chain

MacromoleculeName: Fab 12C2 Heavy Chain / type: other / ID: 2 / Classification: other
Source (natural)Organism: Severe acute respiratory syndrome coronavirus 2
SequenceString: EVQLVESGGG VVQPGGSLRL SCATSGFSFD DCAMHWVRQA PGKGLEWVSL ISGNGGTTYY SDSVKGRFTI SRDSRKNSLY LQMNSLTTED TALYYCATDY QPYSTRWYGS LAGLNYYYYY YGMDVWGQGT AVTVSSASTK GPSVFPLAPS SKSTSGGTAA LGCLVKDYFP ...String:
EVQLVESGGG VVQPGGSLRL SCATSGFSFD DCAMHWVRQA PGKGLEWVSL ISGNGGTTYY SDSVKGRFTI SRDSRKNSLY LQMNSLTTED TALYYCATDY QPYSTRWYGS LAGLNYYYYY YGMDVWGQGT AVTVSSASTK GPSVFPLAPS SKSTSGGTAA LGCLVKDYFP EPVTVSWNSG ALTSGVHTFP AVLQSSGLYS LSSVVTVPSS SLGTQTYICN VNHKPSNTKV DKKVEPKSCD KTHHHHHH
Recombinant expressionOrganism: Homo sapiens (human)

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Macromolecule #3: Fab 12C2 Light Chain

MacromoleculeName: Fab 12C2 Light Chain / type: other / ID: 3 / Classification: other
Source (natural)Organism: Severe acute respiratory syndrome coronavirus 2
SequenceString: DDIQMTQSPS SLSASVGDRV TITCRASQSI SNYLNWYQQK PGKAPKLLIY AASNLQSGVP SRFSGSGSET DFTLTISSLQ PEDFAIYYCQ QSYTAPQAFG QGTKLEIKWY RTVAAPSVFI FPPSDEQLKS GTASVVCLLN NFYPREAKVQ WKVDNALQSG NSQESVTEQD ...String:
DDIQMTQSPS SLSASVGDRV TITCRASQSI SNYLNWYQQK PGKAPKLLIY AASNLQSGVP SRFSGSGSET DFTLTISSLQ PEDFAIYYCQ QSYTAPQAFG QGTKLEIKWY RTVAAPSVFI FPPSDEQLKS GTASVVCLLN NFYPREAKVQ WKVDNALQSG NSQESVTEQD SKDSTYSLSS TLTLSKADYE KHKVYACEVT HQGLSSPVTK SFNRGECS
Recombinant expressionOrganism: Homo sapiens (human)

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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

BufferpH: 8
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeJEOL CRYO ARM 300
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 40.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 0.5 µm

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Image processing

CTF correctionType: PHASE FLIPPING ONLY
Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.02 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: Coot / Number images used: 243370
Initial angle assignmentType: ANGULAR RECONSTITUTION
Final angle assignmentType: ANGULAR RECONSTITUTION
FSC plot (resolution estimation)

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