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- EMDB-25663: SARS-CoV-2 S (Spike Glycoprotein) D614G with Three (3) RBDs Up, B... -

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Basic information

Entry
Database: EMDB / ID: EMD-25663
TitleSARS-CoV-2 S (Spike Glycoprotein) D614G with Three (3) RBDs Up, Bound to Antibody 2-7 scFv, composite map
Map data
Sample
  • Complex: Complex of SARS CoV-2 S, Spike Glycoprotein, variant D614G with Antibody 2-7 scFv
    • Protein or peptide: Spike glycoprotein
  • Protein or peptide: Antibody 2-7 scFv
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
Keywordsvirus / coronavirus / SARS CoV-2 / SARS-CoV-2 / spike / 2-7 / D614G / RBD / 3 RBDs up / three RBDs up / scFv / complex / phage display / VIRAL PROTEIN / local refinement / focused refinement / VIRAL PROTEIN-IMMUNE SYSTEM complex
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 / membrane fusion / receptor-mediated endocytosis of virus by host cell / 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 / Spike glycoprotein S1, N-terminal domain, betacoronavirus-like / Betacoronavirus-like spike glycoprotein S1, N-terminal / Betacoronavirus spike glycoprotein S1, receptor binding / 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 / Escherichia coli (E. coli)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.0 Å
AuthorsByrne PO / McLellan JS
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)R01-AI127521 United States
CitationJournal: Nat Commun / Year: 2022
Title: IgG-like bispecific antibodies with potent and synergistic neutralization against circulating SARS-CoV-2 variants of concern.
Authors: Matthew R Chang / Luke Tomasovic / Natalia A Kuzmina / Adam J Ronk / Patrick O Byrne / Rebecca Johnson / Nadia Storm / Eduardo Olmedillas / Yixuan J Hou / Alexandra Schäfer / Sarah R Leist ...Authors: Matthew R Chang / Luke Tomasovic / Natalia A Kuzmina / Adam J Ronk / Patrick O Byrne / Rebecca Johnson / Nadia Storm / Eduardo Olmedillas / Yixuan J Hou / Alexandra Schäfer / Sarah R Leist / Longping V Tse / Hanzhong Ke / Christian Coherd / Katrina Nguyen / Maliwan Kamkaew / Anna Honko / Quan Zhu / Galit Alter / Erica Ollmann Saphire / Jason S McLellan / Anthony Griffiths / Ralph S Baric / Alexander Bukreyev / Wayne A Marasco /
Abstract: Monoclonal antibodies are a promising approach to treat COVID-19, however the emergence of SARS-CoV-2 variants has challenged the efficacy and future of these therapies. Antibody cocktails are being ...Monoclonal antibodies are a promising approach to treat COVID-19, however the emergence of SARS-CoV-2 variants has challenged the efficacy and future of these therapies. Antibody cocktails are being employed to mitigate these challenges, but neutralization escape remains a major challenge and alternative strategies are needed. Here we present two anti-SARS-CoV-2 spike binding antibodies, one Class 1 and one Class 4, selected from our non-immune human single-chain variable fragment (scFv) phage library, that are engineered into four, fully-human IgG-like bispecific antibodies (BsAb). Prophylaxis of hACE2 mice and post-infection treatment of golden hamsters demonstrates the efficacy of the monospecific antibodies against the original Wuhan strain, while promising in vitro results with the BsAbs demonstrate enhanced binding and distinct synergistic effects on neutralizing activity against circulating variants of concern. In particular, one BsAb engineered in a tandem scFv-Fc configuration shows synergistic neutralization activity against several variants of concern including B.1.617.2. This work provides evidence that synergistic neutralization can be achieved using a BsAb scaffold, and serves as a foundation for the future development of broadly reactive BsAbs against emerging variants of concern.
History
DepositionDec 8, 2021-
Header (metadata) releaseAug 24, 2022-
Map releaseAug 24, 2022-
UpdateJun 19, 2024-
Current statusJun 19, 2024Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_25663.png

Downloads & links

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Map

FileDownload / File: emd_25663.map.gz / Format: CCP4 / Size: 325 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesX (Sec.)Y (Row.)Z (Col.)
0.9 Å/pix.
x 440 pix.
= 396. Å		0.9 Å/pix.
x 440 pix.
= 396. Å		0.9 Å/pix.
x 440 pix.
= 396. Å

Surface

Projections

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Images are generated by Spider.

Voxel sizeX=Y=Z: 0.9 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 8.0
Minimum - Maximum-36.839233 - 64.431380000000004
Average (Standard dev.)0.012405212 (±1.2419266)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderZYX
Origin000
Dimensions440440440
Spacing440440440
CellA=B=C: 396.00003 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_25663_msk_1.map
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Mask #2

Fileemd_25663_msk_2.map
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Mask #3

Fileemd_25663_msk_3.map
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Additional map: #5

Fileemd_25663_additional_1.map
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Additional map: #4

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Additional map: #3

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Additional map: #2

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Additional map: #1

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Half map: #2

Fileemd_25663_half_map_1.map
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Sample components

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Entire : Complex of SARS CoV-2 S, Spike Glycoprotein, variant D614G with A...

EntireName: Complex of SARS CoV-2 S, Spike Glycoprotein, variant D614G with Antibody 2-7 scFv
Components
  • Complex: Complex of SARS CoV-2 S, Spike Glycoprotein, variant D614G with Antibody 2-7 scFv
    • Protein or peptide: Spike glycoprotein
  • Protein or peptide: Antibody 2-7 scFv
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose

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Supramolecule #1: Complex of SARS CoV-2 S, Spike Glycoprotein, variant D614G with A...

SupramoleculeName: Complex of SARS CoV-2 S, Spike Glycoprotein, variant D614G with Antibody 2-7 scFv
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1

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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: 127.00293 KDa
Recombinant expressionOrganism: Cricetulus griseus (Chinese hamster)
SequenceString: MFVFLVLLPL VSSQCVNLTT RTQLPPAYTN SFTRGVYYPD KVFRSSVLHS TQDLFLPFFS NVTWFHAIHV SGTNGTKRFD NPVLPFNDG VYFASTEKSN IIRGWIFGTT LDSKTQSLLI VNNATNVVIK VCEFQFCNDP FLGVYYHKNN KSWMESEFRV Y SSANNCTF ...String:
MFVFLVLLPL VSSQCVNLTT RTQLPPAYTN SFTRGVYYPD KVFRSSVLHS TQDLFLPFFS NVTWFHAIHV SGTNGTKRFD NPVLPFNDG VYFASTEKSN IIRGWIFGTT LDSKTQSLLI VNNATNVVIK VCEFQFCNDP FLGVYYHKNN KSWMESEFRV Y SSANNCTF EYVSQPFLMD LEGKQGNFKN LREFVFKNID GYFKIYSKHT PINLVRDLPQ GFSALEPLVD LPIGINITRF QT LLALHRS YLTPGDSSSG WTAGAAAYYV GYLQPRTFLL KYNENGTITD AVDCALDPLS ETKCTLKSFT VEKGIYQTSN FRV QPTESI VRFPNITNLC PFGEVFNATR FASVYAWNRK RISNCVADYS VLYNSASFST FKCYGVSPTK LNDLCFTNVY ADSF VIRGD EVRQIAPGQT GKIADYNYKL PDDFTGCVIA WNSNNLDSKV GGNYNYLYRL FRKSNLKPFE RDISTEIYQA GSTPC NGVE GFNCYFPLQS YGFQPTNGVG YQPYRVVVLS FELLHAPATV CGPKKSTNLV KNKCVNFNFN GLTGTGVLTE SNKKFL PFQ QFGRDIADTT DAVRDPQTLE ILDITPCSFG GVSVITPGTN TSNQVAVLYQ GVNCTEVPVA IHADQLTPTW RVYSTGS NV FQTRAGCLIG AEHVNNSYEC DIPIGAGICA SYQTQTNSPG SASSVASQSI IAYTMSLGAE NSVAYSNNSI AIPTNFTI S VTTEILPVSM TKTSVDCTMY ICGDSTECSN LLLQYGSFCT QLNRALTGIA VEQDKNTQEV FAQVKQIYKT PPIKDFGGF NFSQILPDPS KPSKRSFIED LLFNKVTLAD AGFIKQYGDC LGDIAARDLI CAQKFNGLTV LPPLLTDEMI AQYTSALLAG TITSGWTFG AGAALQIPFA MQMAYRFNGI GVTQNVLYEN QKLIANQFNS AIGKIQDSLS STASALGKLQ DVVNQNAQAL N TLVKQLSS NFGAISSVLN DILSRLDPPE AEVQIDRLIT GRLQSLQTYV TQQLIRAAEI RASANLAATK MSECVLGQSK RV DFCGKGY HLMSFPQSAP HGVVFLHVTY VPAQEKNFTT APAICHDGKA HFPREGVFVS NGTHWFVTQR NFYEPQIITT DNT FVSGNC DVVIGIVNNT VYDPLQPELD SFK

UniProtKB: Spike glycoprotein

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Macromolecule #2: Antibody 2-7 scFv

MacromoleculeName: Antibody 2-7 scFv / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Escherichia coli (E. coli)
Molecular weightTheoretical: 30.570977 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MKHLWFFLLL VAAAQPAMAQ VTLKESGPTR VKPTQTLTLT CTFSGFSLST TGVGVGWIRQ PPGKALEWLA LIYWNDDKRY SPSLKSRLT ITKDTSKNQV VLTMTNMDPV DTATYYCARI SGSGYFYPFD IWGQGTTVTV SSGGGGSGGG GSGGGGSNFM L TQPHSVSE ...String:
MKHLWFFLLL VAAAQPAMAQ VTLKESGPTR VKPTQTLTLT CTFSGFSLST TGVGVGWIRQ PPGKALEWLA LIYWNDDKRY SPSLKSRLT ITKDTSKNQV VLTMTNMDPV DTATYYCARI SGSGYFYPFD IWGQGTTVTV SSGGGGSGGG GSGGGGSNFM L TQPHSVSE SPGKTVTISC TRSSGSIASN YVQWYQQRPG SSPTTVIYED NQRPSGVPDR FSGSIDSSSN SASLTISGLK AE DEADYYC QSYDSSSLWV FGGGTKLTVL GQPKAAPSAA ALEHHHHHH

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Macromolecule #4: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 4 / Number of copies: 45 / 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: 8
Component:
ConcentrationNameFormula
2.0 mMTris base
200.0 mMsodium chlorideNaCl
GridModel: UltrAuFoil R1.2/1.3 / Material: GOLD / Mesh: 300 / Support film - Material: GOLD / Support film - topology: HOLEY / Pretreatment - Type: PLASMA CLEANING / Pretreatment - Time: 180 sec. / Pretreatment - Atmosphere: OTHER
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 (6k x 4k) / Average electron dose: 70.0 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: 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:

7k8y

Final reconstructionApplied symmetry - Point group: C3 (3 fold cyclic) / Resolution.type: BY AUTHOR / Resolution: 3.0 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 17708
Initial angle assignmentType: OTHER
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

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