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- EMDB-34406: Local refinement of SARS-CoV-2 Omicron BA.1 Spike glycoprotein in... -

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Basic information

Entry
Database: EMDB / ID: EMD-34406
TitleLocal refinement of SARS-CoV-2 Omicron BA.1 Spike glycoprotein in complex with rabbit monoclonal antibody 1H1 Fab
Map data
Sample
  • Complex: SARS-CoV-2 Omicron spike glycoprotein complex with 55A8 Fab
    • Complex: Omicron spike glycoprotein
      • Protein or peptide: Spike protein S1
    • Complex: 1H1 Fab
      • Protein or peptide: rabbit monoclonal antibody 1H1 Fab light chain
      • Protein or peptide: rabbit monoclonal antibody 1H1 Fab heavy chain
KeywordsVIRAL 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 / identical protein binding / membrane / 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 speciesSevere acute respiratory syndrome coronavirus 2 / Oryctolagus cuniculus (rabbit)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.52 Å
AuthorsGuo H / Gao Y / Lu Y / Yang H / Ji X
Funding support China, 1 items
OrganizationGrant numberCountry
Other government China
CitationJournal: Commun Biol / Year: 2023
Title: Mechanism of a rabbit monoclonal antibody broadly neutralizing SARS-CoV-2 variants.
Authors: Hangtian Guo / Yixuan Yang / Tiantian Zhao / Yuchi Lu / Yan Gao / Tinghan Li / Hang Xiao / Xiaoyu Chu / Le Zheng / Wanting Li / Hao Cheng / Haibin Huang / Yang Liu / Yang Lou / Henry C ...Authors: Hangtian Guo / Yixuan Yang / Tiantian Zhao / Yuchi Lu / Yan Gao / Tinghan Li / Hang Xiao / Xiaoyu Chu / Le Zheng / Wanting Li / Hao Cheng / Haibin Huang / Yang Liu / Yang Lou / Henry C Nguyen / Chao Wu / Yuxin Chen / Haitao Yang / Xiaoyun Ji /
Abstract: Due to the continuous evolution of SARS-CoV-2, the Omicron variant has emerged and exhibits severe immune evasion. The high number of mutations at key antigenic sites on the spike protein has made a ...Due to the continuous evolution of SARS-CoV-2, the Omicron variant has emerged and exhibits severe immune evasion. The high number of mutations at key antigenic sites on the spike protein has made a large number of existing antibodies and vaccines ineffective against this variant. Therefore, it is urgent to develop efficient broad-spectrum neutralizing therapeutic drugs. Here we characterize a rabbit monoclonal antibody (RmAb) 1H1 with broad-spectrum neutralizing potency against Omicron sublineages including BA.1, BA.1.1, BA.2, BA.2.12.1, BA.2.75, BA.3 and BA.4/5. Cryo-electron microscopy (cryo-EM) structure determination of the BA.1 spike-1H1 Fab complexes shows that 1H1 targets a highly conserved region of RBD and avoids most of the circulating Omicron mutations, explaining its broad-spectrum neutralization potency. Our findings indicate 1H1 as a promising RmAb model for designing broad-spectrum neutralizing antibodies and shed light on the development of therapeutic agents as well as effective vaccines against newly emerging variants in the future.
History
DepositionSep 27, 2022-
Header (metadata) releaseApr 12, 2023-
Map releaseApr 12, 2023-
UpdateJun 25, 2025-
Current statusJun 25, 2025Processing site: PDBj / Status: Released

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Structure visualization

Supplemental images

emd_34406.png

Downloads & links

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Map

FileDownload / File: emd_34406.map.gz / Format: CCP4 / Size: 512 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

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AxesZ (Sec.)Y (Row.)X (Col.)
0.83 Å/pix.
x 512 pix.
= 425.984 Å		0.83 Å/pix.
x 512 pix.
= 425.984 Å		0.83 Å/pix.
x 512 pix.
= 425.984 Å

Surface

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Images are generated by Spider.

Voxel sizeX=Y=Z: 0.832 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.4006
Minimum - Maximum-0.83817303 - 1.9092126
Average (Standard dev.)-0.0031586455 (±0.02693969)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions512512512
Spacing512512512
CellA=B=C: 425.984 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #2

Fileemd_34406_half_map_1.map
Projections & Slices
AxesZYX

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Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #1

Fileemd_34406_half_map_2.map
Projections & Slices
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Sample components

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Entire : SARS-CoV-2 Omicron spike glycoprotein complex with 55A8 Fab

EntireName: SARS-CoV-2 Omicron spike glycoprotein complex with 55A8 Fab
Components
  • Complex: SARS-CoV-2 Omicron spike glycoprotein complex with 55A8 Fab
    • Complex: Omicron spike glycoprotein
      • Protein or peptide: Spike protein S1
    • Complex: 1H1 Fab
      • Protein or peptide: rabbit monoclonal antibody 1H1 Fab light chain
      • Protein or peptide: rabbit monoclonal antibody 1H1 Fab heavy chain

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Supramolecule #1: SARS-CoV-2 Omicron spike glycoprotein complex with 55A8 Fab

SupramoleculeName: SARS-CoV-2 Omicron spike glycoprotein complex with 55A8 Fab
type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Severe acute respiratory syndrome coronavirus 2

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Supramolecule #2: Omicron spike glycoprotein

SupramoleculeName: Omicron spike glycoprotein / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1
Details: SARS-CoV-2 Omicron BA.1 variant spike protein receptor binding domain
Source (natural)Organism: Severe acute respiratory syndrome coronavirus 2

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Supramolecule #3: 1H1 Fab

SupramoleculeName: 1H1 Fab / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2-#3
Details: Fab fragment generated by proteolytic cleavage of IgG antibody

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Macromolecule #1: Spike protein S1

MacromoleculeName: Spike protein S1 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Severe acute respiratory syndrome coronavirus 2
Molecular weightTheoretical: 22.065934 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: NLCPFDEVFN ATRFASVYAW NRKRISNCVA DYSVLYNLAP FFTFKCYGVS PTKLNDLCFT NVYADSFVIR GDEVRQIAPG QTGNIADYN YKLPDDFTGC VIAWNSNKLD SKVSGNYNYL YRLFRKSNLK PFERDISTEI YQAGNKPCNG VAGFNCYFPL R SYSFRPTY ...String:
NLCPFDEVFN ATRFASVYAW NRKRISNCVA DYSVLYNLAP FFTFKCYGVS PTKLNDLCFT NVYADSFVIR GDEVRQIAPG QTGNIADYN YKLPDDFTGC VIAWNSNKLD SKVSGNYNYL YRLFRKSNLK PFERDISTEI YQAGNKPCNG VAGFNCYFPL R SYSFRPTY GVGHQPYRVV VLSFELLHAP ATVCGP

UniProtKB: Spike glycoprotein

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Macromolecule #2: rabbit monoclonal antibody 1H1 Fab light chain

MacromoleculeName: rabbit monoclonal antibody 1H1 Fab light chain / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Oryctolagus cuniculus (rabbit)
Molecular weightTheoretical: 11.739082 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
DIVMTQTPAS VSEPVGGTVT IKCQASESIS NWLAWYQQKP GQPPKLLIYA AFTLASGVPS RFKGSGSGTQ FTLTINGVEC ADAATYYCQ QTYSSRDVDN VFGGGTEVVV KG

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Macromolecule #3: rabbit monoclonal antibody 1H1 Fab heavy chain

MacromoleculeName: rabbit monoclonal antibody 1H1 Fab heavy chain / type: protein_or_peptide / ID: 3 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Oryctolagus cuniculus (rabbit)
Molecular weightTheoretical: 12.863201 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
QSLEESGGDL VKPGASLTLT CTASGFSFSS GYDMCWVRQA PGKGLEWIAC IGTGSSGNIY YASWAKGRFT ISKTSSTTVT LQMTSLTAA DTATYFCARD DADYAGPDYF NLWGPGTLVT VSS

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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: 7.4
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 60.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: SPOT SCAN / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.8000000000000003 µm / Nominal defocus min: 1.2 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.52 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 207777
Initial angle assignmentType: COMMON LINE
Final angle assignmentType: COMMON LINE

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