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- EMDB-37240: SARS-CoV-2 Omicron spike in complex with 5817 Fab -

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Basic information

Entry
Database: EMDB / ID: EMD-37240
TitleSARS-CoV-2 Omicron spike in complex with 5817 Fab
Map data
Sample
  • Complex: SARS-CoV-2 Omicron spike in complex with 5817 Fab
    • Protein or peptide: Spike glycoprotein
    • Protein or peptide: Heavy chain of 5817 Fab
    • Protein or peptide: Light chain of 5817 Fab
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
  • Ligand: water
KeywordsSARS-CoV-2 / omicron / RBD / Fab / VIRAL PROTEIN
Function / homology
Function and homology information


Maturation of spike protein / viral translation / Translation of Structural Proteins / Virion Assembly and Release / host cell surface / host extracellular space / suppression by virus of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion / entry receptor-mediated virion attachment to host cell ...Maturation of spike protein / viral translation / Translation of Structural Proteins / Virion Assembly and Release / host cell surface / host extracellular space / suppression by virus of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion / entry receptor-mediated virion attachment to host cell / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / receptor-mediated endocytosis of virus by host cell / membrane fusion / Attachment and Entry / positive regulation of viral entry into host cell / receptor-mediated virion attachment to host cell / receptor ligand activity / host cell surface receptor binding / symbiont-mediated suppression of host innate immune response / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / SARS-CoV-2 activates/modulates innate and adaptive immune responses / host cell plasma membrane / 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, betacoronavirus / Spike glycoprotein, N-terminal domain superfamily / Betacoronavirus spike (S) glycoprotein S1 subunit N-terminal (NTD) domain profile. / Betacoronavirus spike (S) glycoprotein S1 subunit C-terminal (CTD) domain profile. / Spike (S) protein S1 subunit, receptor-binding domain, betacoronavirus / Spike S1 subunit, receptor binding domain superfamily, betacoronavirus ...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, betacoronavirus / Spike glycoprotein, N-terminal domain superfamily / Betacoronavirus spike (S) glycoprotein S1 subunit N-terminal (NTD) domain profile. / Betacoronavirus spike (S) glycoprotein S1 subunit C-terminal (CTD) domain profile. / Spike (S) protein S1 subunit, receptor-binding domain, betacoronavirus / Spike S1 subunit, receptor binding domain superfamily, betacoronavirus / Betacoronavirus spike glycoprotein S1, receptor binding / Spike glycoprotein S1, N-terminal domain, betacoronavirus-like / Betacoronavirus-like spike glycoprotein S1, N-terminal / 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 superfamily, coronavirus / Spike glycoprotein S2, coronavirus / Coronavirus spike glycoprotein S2
Similarity search - Domain/homology
Biological speciesSevere acute respiratory syndrome coronavirus 2 / Homo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.0 Å
AuthorsCao L / Wang X
Funding support1 items
OrganizationGrant numberCountry
Not funded
CitationJournal: Cell Rep / Year: 2024
Title: Identification of a broad sarbecovirus neutralizing antibody targeting a conserved epitope on the receptor-binding domain.
Authors: Yanqun Wang / Zhaoyong Zhang / Minnan Yang / Xinyi Xiong / Qihong Yan / Lei Cao / Peilan Wei / Yuting Zhang / Lu Zhang / Kexin Lv / Jiantao Chen / Xuesong Liu / Xiaochu Zhao / Juxue Xiao / ...Authors: Yanqun Wang / Zhaoyong Zhang / Minnan Yang / Xinyi Xiong / Qihong Yan / Lei Cao / Peilan Wei / Yuting Zhang / Lu Zhang / Kexin Lv / Jiantao Chen / Xuesong Liu / Xiaochu Zhao / Juxue Xiao / Shengnan Zhang / Airu Zhu / Mian Gan / Jingjun Zhang / Ruoxi Cai / Jianfen Zhuo / Yanjun Zhang / Haiyue Rao / Bin Qu / Yuanyuan Zhang / Lei Chen / Jun Dai / Linling Cheng / Qingtao Hu / Yaoqing Chen / Huibin Lv / Ray T Y So / Malik Peiris / Jingxian Zhao / Xiaoqing Liu / Chris Ka Pun Mok / Xiangxi Wang / Jincun Zhao /
Abstract: Omicron, as the emerging variant with enhanced vaccine tolerance, has sharply disrupted most therapeutic antibodies. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) belongs to the ...Omicron, as the emerging variant with enhanced vaccine tolerance, has sharply disrupted most therapeutic antibodies. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) belongs to the subgenus Sarbecovirus, members of which share high sequence similarity. Herein, we report one sarbecovirus antibody, 5817, which has broad-spectrum neutralization capacity against SARS-CoV-2 variants of concern (VOCs) and SARS-CoV, as well as related bat and pangolin viruses. 5817 can hardly compete with six classes of receptor-binding-domain-targeted antibodies grouped by structural classifications. No obvious impairment in the potency is detected against SARS-CoV-2 Omicron and subvariants. The cryoelectron microscopy (cryo-EM) structure of neutralizing antibody 5817 in complex with Omicron spike reveals a highly conserved epitope, only existing at the receptor-binding domain (RBD) open state. Prophylactic and therapeutic administration of 5817 potently protects mice from SARS-CoV-2 Beta, Delta, Omicron, and SARS-CoV infection. This study reveals a highly conserved cryptic epitope targeted by a broad sarbecovirus neutralizing antibody, which would be beneficial to meet the potential threat of pre-emergent SARS-CoV-2 VOCs.
History
DepositionAug 21, 2023-
Header (metadata) releaseApr 17, 2024-
Map releaseApr 17, 2024-
UpdateNov 13, 2024-
Current statusNov 13, 2024Processing site: PDBj / Status: Released

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Structure visualization

Supplemental images

emd_37240.png

Downloads & links

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Map

FileDownload / File: emd_37240.map.gz / Format: CCP4 / Size: 178 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.06 Å/pix.
x 360 pix.
= 381.6 Å		1.06 Å/pix.
x 360 pix.
= 381.6 Å		1.06 Å/pix.
x 360 pix.
= 381.6 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.06 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.45
Minimum - Maximum-4.4373565 - 7.6491923
Average (Standard dev.)-0.004013566 (±0.115486)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions360360360
Spacing360360360
CellA=B=C: 381.59998 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #2

Fileemd_37240_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #1

Fileemd_37240_half_map_2.map
Projections & Slices
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Slices (1/2)
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Histogram

Histogram (log scale)

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Sample components

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Entire : SARS-CoV-2 Omicron spike in complex with 5817 Fab

EntireName: SARS-CoV-2 Omicron spike in complex with 5817 Fab
Components
  • Complex: SARS-CoV-2 Omicron spike in complex with 5817 Fab
    • Protein or peptide: Spike glycoprotein
    • Protein or peptide: Heavy chain of 5817 Fab
    • Protein or peptide: Light chain of 5817 Fab
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
  • Ligand: water

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Supramolecule #1: SARS-CoV-2 Omicron spike in complex with 5817 Fab

SupramoleculeName: SARS-CoV-2 Omicron spike in complex with 5817 Fab / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3
Source (natural)Organism: Severe acute respiratory syndrome coronavirus 2

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Macromolecule #1: Spike glycoprotein

MacromoleculeName: Spike glycoprotein / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Severe acute respiratory syndrome coronavirus 2
Molecular weightTheoretical: 124.547477 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: AYTNSFTRGV YYPDKVFRSS VLHSTQDLFL PFFSNVTWFH VIHVSGTNGT KRFDNPVLPF NDGVYFASIE KSNIIRGWIF GTTLDSKTQ SLLIVNNATN VVIKVCEFQF CNDPFLDVYY HKNNKSWMES DFRVYSSANN CTFEYVSQPF LMDLEGKQGN F KNLREFVF ...String:
AYTNSFTRGV YYPDKVFRSS VLHSTQDLFL PFFSNVTWFH VIHVSGTNGT KRFDNPVLPF NDGVYFASIE KSNIIRGWIF GTTLDSKTQ SLLIVNNATN VVIKVCEFQF CNDPFLDVYY HKNNKSWMES DFRVYSSANN CTFEYVSQPF LMDLEGKQGN F KNLREFVF KNIDGYFKIY SKHTPINLVR DLPQGFSALE PLVDLPIGIN ITRFQTLLAL HRSYLTPGDS SSGWTAGAAA YY VGYLQPR TFLLKYNENG TITDAVDCAL DPLSETKCTL KSFTVEKGIY QTSNFRVQPT ESIVRFPNIT NLCPFDEVFN ATR FASVYA WNRKRISNCV ADYSVLYNLA PFFTFKCYGV SPTKLNDLCF TNVYADSFVI RGDEVRQIAP GQTGNIADYN YKLP DDFTG CVIAWNSNKL DSKVSGNYNY LYRLFRKSNL KPFERDISTE IYQAGNKPCN GVAGFNCYFP LRSYSFRPTY GVGHQ PYRV VVLSFELLHA PATVCGPKKS TNLVKNKCVN FNFNGLKGTG VLTESNKKFL PFQQFGRDIA DTTDAVRDPQ TLEILD ITP CSFGGVSVIT PGTNTSNQVA VLYQGVNCTE VPVAIHADQL TPTWRVYSTG SNVFQTRAGC LIGAEYVNNS YECDIPI GA GICASYQTQT NSPRRARSVA SQSIIAYTMS LGAENSVAYS NNSIAIPTNF TISVTTEILP VSMTKTSVDC TMYICGDS T ECSNLLLQYG SFCTQLKRAL TGIAVEQDKN TQEVFAQVKQ IYKTPPIKYF GGFNFSQILP DPSKPSKRSF IEDLLFNKV TLADAGFIKQ YGDCLGDIAA RDLICAQKFK GLTVLPPLLT DEMIAQYTSA LLAGTITSGW TFGAGAALQI PFAMQMAYRF NGIGVTQNV LYENQKLIAN QFNSAIGKIQ DSLSSTASAL GKLQDVVNHN AQALNTLVKQ LSSKFGAISS VLNDIFSRLD P PEAEVQID RLITGRLQSL QTYVTQQLIR AAEIRASANL AATKMSECVL GQSKRVDFCG KGYHLMSFPQ SAPHGVVFLH VT YVPAQEK NFTTAPAICH DGKAHFPREG VFVSNGTHWF VTQRNFYEPQ IITTDNTFVS GNCDVVIGIV NNTVYDPLQP ELD

UniProtKB: Spike glycoprotein

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Macromolecule #2: Heavy chain of 5817 Fab

MacromoleculeName: Heavy chain of 5817 Fab / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 13.387045 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
EVQLVESGGG LVKPGGSLRL SCAASGFSFS DAWMSWVRQA PGKGLEWVGR VSSEIGGGTT DYAAPVKGRF TISRDDSKNT LFLQMSSLK TEDTAVYYCT TGVDIVVMMY ADDAFDIWGQ GTMVTV

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Macromolecule #3: Light chain of 5817 Fab

MacromoleculeName: Light chain of 5817 Fab / type: protein_or_peptide / ID: 3 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 11.470526 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
ELTQDPAVSV ALGQTVRITC QGDSLRSYYA SWYQQKPGQA PVLVIYGKNN RPSGIPDRFS GSSSGNTASL TITGPQAEDE ADYYCTSRD SSGNHVIFGG GTKLTVLGQ

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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: 36 / Formula: NAG
Molecular weightTheoretical: 221.208 Da
Chemical component information

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

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Macromolecule #6: water

MacromoleculeName: water / type: ligand / ID: 6 / Number of copies: 58 / Formula: HOH
Molecular weightTheoretical: 18.015 Da
Chemical component information

ChemComp-HOH:
WATER

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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: 7.5
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: 45.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.5 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Startup modelType of model: PDB ENTRY
PDB model - PDB ID:

6vxx

Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.0 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 5129
Initial angle assignmentType: ANGULAR RECONSTITUTION
Final angle assignmentType: ANGULAR RECONSTITUTION

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