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- EMDB-25166: Antibody 10-28 in complex with prefusion SARS-CoV-2 B.1.351 Spike... -

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Basic information

Entry
Database: EMDB / ID: EMD-25166
TitleAntibody 10-28 in complex with prefusion SARS-CoV-2 B.1.351 Spike glycoprotein
Map data
Sample
  • Complex: Antibody 10-28 in complex with prefusion SARS-CoV-2 B.1.351 Spike glycoprotein
    • Protein or peptide: spike glycoprotein
    • Protein or peptide: antibody 10-28 heavy
    • Protein or peptide: antibody 10-28 light
Keywordsspike glycoprotein / antibody / VIRAL PROTEIN
Biological speciesSevere acute respiratory syndrome coronavirus 2 / Homo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 6.5 Å
AuthorsCasner RG / Shapiro L
Funding support China, 1 items
OrganizationGrant numberCountry
Jack Ma Foundation China
CitationJournal: Sci Transl Med / Year: 2022
Title: An antibody class with a common CDRH3 motif broadly neutralizes sarbecoviruses.
Authors: Lihong Liu / Sho Iketani / Yicheng Guo / Eswar R Reddem / Ryan G Casner / Manoj S Nair / Jian Yu / Jasper F-W Chan / Maple Wang / Gabriele Cerutti / Zhiteng Li / Nicholas C Morano / Candace ...Authors: Lihong Liu / Sho Iketani / Yicheng Guo / Eswar R Reddem / Ryan G Casner / Manoj S Nair / Jian Yu / Jasper F-W Chan / Maple Wang / Gabriele Cerutti / Zhiteng Li / Nicholas C Morano / Candace D Castagna / Laura Corredor / Hin Chu / Shuofeng Yuan / Vincent Kwok-Man Poon / Chris Chun-Sing Chan / Zhiwei Chen / Yang Luo / Marcus Cunningham / Alejandro Chavez / Michael T Yin / David S Perlin / Moriya Tsuji / Kwok-Yung Yuen / Peter D Kwong / Zizhang Sheng / Yaoxing Huang / Lawrence Shapiro / David D Ho /
Abstract: The devastation caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made clear the importance of pandemic preparedness. To address future zoonotic outbreaks due to related ...The devastation caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made clear the importance of pandemic preparedness. To address future zoonotic outbreaks due to related viruses in the sarbecovirus subgenus, we identified a human monoclonal antibody, 10-40, that neutralized or bound all sarbecoviruses tested in vitro and protected against SARS-CoV-2 and SARS-CoV in vivo. Comparative studies with other receptor-binding domain (RBD)-directed antibodies showed 10-40 to have the greatest breadth against sarbecoviruses, suggesting that 10-40 is a promising agent for pandemic preparedness. Moreover, structural analyses on 10-40 and similar antibodies not only defined an epitope cluster in the inner face of the RBD that is well conserved among sarbecoviruses but also uncovered a distinct antibody class with a common CDRH3 motif. Our analyses also suggested that elicitation of this class of antibodies may not be overly difficult, an observation that bodes well for the development of a pan-sarbecovirus vaccine.
History
DepositionOct 19, 2021-
Header (metadata) releaseMay 4, 2022-
Map releaseMay 4, 2022-
UpdateJan 17, 2024-
Current statusJan 17, 2024Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_25166.png

Downloads & links

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Map

FileDownload / File: emd_25166.map.gz / Format: CCP4 / Size: 216 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Voxel sizeX=Y=Z: 1.07 Å
Density
Contour LevelBy AUTHOR: 0.14
Minimum - Maximum-0.18553735 - 0.5738451
Average (Standard dev.)-0.0014018021 (±0.021089965)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions384384384
Spacing384384384
CellA=B=C: 410.88 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #2

Fileemd_25166_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_25166_half_map_2.map
Projections & Slices
AxesZYX

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Slices (1/2)
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Histogram (log scale)

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Sample components

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Entire : Antibody 10-28 in complex with prefusion SARS-CoV-2 B.1.351 Spike...

EntireName: Antibody 10-28 in complex with prefusion SARS-CoV-2 B.1.351 Spike glycoprotein
Components
  • Complex: Antibody 10-28 in complex with prefusion SARS-CoV-2 B.1.351 Spike glycoprotein
    • Protein or peptide: spike glycoprotein
    • Protein or peptide: antibody 10-28 heavy
    • Protein or peptide: antibody 10-28 light

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Supramolecule #1: Antibody 10-28 in complex with prefusion SARS-CoV-2 B.1.351 Spike...

SupramoleculeName: Antibody 10-28 in complex with prefusion SARS-CoV-2 B.1.351 Spike glycoprotein
type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
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 / Enantiomer: LEVO
Source (natural)Organism: Severe acute respiratory syndrome coronavirus 2
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MFVFLVLLPL VSSQCVNFTT RTQLPPAYTN SFTRGVYYPD KVFRSSVLHS TQDLFLPFFS NVTWFHAIHV SGTNGTKRFA NPVLPFNDGV YFASTEKSNI IRGWIFGTTL DSKTQSLLIV NNATNVVIKV CEFQFCNDPF LGVYYHKNNK SWMESEFRVY SSANNCTFEY ...String:
MFVFLVLLPL VSSQCVNFTT RTQLPPAYTN SFTRGVYYPD KVFRSSVLHS TQDLFLPFFS NVTWFHAIHV SGTNGTKRFA NPVLPFNDGV YFASTEKSNI IRGWIFGTTL DSKTQSLLIV NNATNVVIKV CEFQFCNDPF LGVYYHKNNK SWMESEFRVY SSANNCTFEY VSQPFLMDLE GKQGNFKNLR EFVFKNIDGY FKIYSKHTPI NLVRGLPQGF SALEPLVDLP IGINITRFQT LHISYLTPGD SSSGWTAGAA AYYVGYLQPR TFLLKYNENG TITDAVDCAL DPLSETKCTL KSFTVEKGIY QTSNFRVQPT ESIVRFPNIT NLCPFGEVFN ATRFASVYAW NRKRISNCVA DYSVLYNSAS FSTFKCYGVS PTKLNDLCFT NVYADSFVIR GDEVRQIAPG QTGNIADYNY KLPDDFTGCV IAWNSNNLDS KVGGNYNYLY RLFRKSNLKP FERDISTEIY QAGSTPCNGV KGFNCYFPLQ SYGFQPTYGV GYQPYRVVVL SFELLHAPAT VCGPKKSTNL VKNKCVNFNF NGLTGTGVLT ESNKKFLPFQ QFGRDIADTT DAVRDPQTLE ILDITPCSFG GVSVITPGTN TSNQVAVLYQ GVNCTEVPVA IHADQLTPTW RVYSTGSNVF QTRAGCLIGA EHVNNSYECD IPIGAGICAS YQTQTNSPGS ASSVASQSII AYTMSLGVEN SVAYSNNSIA IPTNFTISVT TEILPVSMTK TSVDCTMYIC GDSTECSNLL LQYGSFCTQL NRALTGIAVE QDKNTQEVFA QVKQIYKTPP IKDFGGFNFS QILPDPSKPS KRSFIEDLLF NKVTLADAGF IKQYGDCLGD IAARDLICAQ KFNGLTVLPP LLTDEMIAQY TSALLAGTIT SGWTFGAGAA LQIPFAMQMA YRFNGIGVTQ NVLYENQKLI ANQFNSAIGK IQDSLSSTAS ALGKLQDVVN QNAQALNTLV KQLSSNFGAI SSVLNDILSR LDPPEAEVQI DRLITGRLQS LQTYVTQQLI RAAEIRASAN LAATKMSECV LGQSKRVDFC GKGYHLMSFP QSAPHGVVFL HVTYVPAQEK NFTTAPAICH DGKAHFPREG VFVSNGTHWF VTQRNFYEPQ IITTDNTFVS GNCDVVIGIV NNTVYDPLQP ELDSFKEELD KYFKNHTSPD VDLGDISGIN ASVVNIQKEI DRLNEVAKNL NESLIDLQEL GKYEQ

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Macromolecule #2: antibody 10-28 heavy

MacromoleculeName: antibody 10-28 heavy / type: protein_or_peptide / ID: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
QVQLVESGGG VVQPGRSLRL SCAASGFTFS SYDMHWVRQA PGKGLEWVAV ISYDGSSKFY AESVKGRFT ISRDNSKNTL YLQMNSLRAE ETAVYYCVKD GEQLVPLFDY WGQGTLVTVS S

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Macromolecule #3: antibody 10-28 light

MacromoleculeName: antibody 10-28 light / type: protein_or_peptide / ID: 3 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
DIQMTQSPSS LSASVGDRVT ITCRASQSIS SYLNWYQQKP GKAPKLLIYA ASSLQSGVPS RFSGSGSGT DFTLTISSLQ PEDFATYYCQ QSYSTPGVTF GPGTKVDIK

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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

Concentration1 mg/mL
BufferpH: 5.5
Component:
ConcentrationFormulaName
150.0 mMNaClSodium Chloride
10.0 mMSodium Acetate
0.005 % (w/v)DDM
GridModel: C-flat-1.2/1.3 / Mesh: 300 / Pretreatment - Type: GLOW DISCHARGE
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 293 K / Instrument: FEI VITROBOT MARK IV

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average exposure time: 2.4 sec. / Average electron dose: 42.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Startup modelType of model: OTHER / Details: Ab initio
Final reconstructionResolution.type: BY AUTHOR / Resolution: 6.5 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC (ver. v3.2.0)
Details: Value reported by cryoSPARC FSC calculation with a "loose" mask.
Number images used: 251871
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

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