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- EMDB-23523: SARS-2 CoV 6P Mut7 in complex with Fab J08 -

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Basic information

Entry
Database: EMDB / ID: EMD-23523
TitleSARS-2 CoV 6P Mut7 in complex with Fab J08
Map dataSARS-2 CoV 6P Mut7 in complex with Fab J08
Sample
  • Complex: SARS-2 CoV 6P Mut7 Spike Protein in complex with Fab J08
    • Complex: fragment antigent binding (Fab) J08
    • Complex: SARS-2 CoV 6P Mut7 Spike 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 / host cell endoplasmic reticulum-Golgi intermediate compartment membrane ...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 / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / entry receptor-mediated virion attachment to host cell / receptor-mediated endocytosis of virus by host cell / Attachment and Entry / membrane fusion / positive regulation of viral entry into host cell / receptor-mediated virion attachment to host cell / receptor ligand activity / host cell surface receptor binding / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / virion attachment to host cell / SARS-CoV-2 activates/modulates innate and adaptive immune responses / host cell plasma membrane / virion membrane / membrane / identical protein binding / 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 / Betacoronavirus spike (S) glycoprotein S1 subunit N-terminal (NTD) domain profile. / Spike glycoprotein, N-terminal domain superfamily / Betacoronavirus spike (S) glycoprotein S1 subunit C-terminal (CTD) domain profile. / Spike glycoprotein, betacoronavirus / 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 ...Spike (S) protein S1 subunit, receptor-binding domain, SARS-CoV-2 / Spike (S) protein S1 subunit, N-terminal domain, SARS-CoV-like / Betacoronavirus spike (S) glycoprotein S1 subunit N-terminal (NTD) domain profile. / Spike glycoprotein, N-terminal domain superfamily / Betacoronavirus spike (S) glycoprotein S1 subunit C-terminal (CTD) domain profile. / Spike glycoprotein, betacoronavirus / 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 2 (HR2) region profile. / Coronavirus spike (S) glycoprotein S2 subunit heptad repeat 1 (HR1) region profile. / Spike glycoprotein S2 superfamily, coronavirus / Spike glycoprotein S2, coronavirus / Coronavirus spike glycoprotein S2 / Coronavirus spike glycoprotein S1, C-terminal / Coronavirus spike glycoprotein S1, C-terminal
Similarity search - Domain/homology
Biological speciesHomo sapiens (human) / Severe acute respiratory syndrome coronavirus 2
Methodsingle particle reconstruction / negative staining / Resolution: 29.0 Å
AuthorsTorres JL / Ward AB
Funding support United States, 1 items
OrganizationGrant numberCountry
Not funded United States
CitationJournal: Cell / Year: 2021
Title: Extremely potent human monoclonal antibodies from COVID-19 convalescent patients.
Authors: Emanuele Andreano / Emanuele Nicastri / Ida Paciello / Piero Pileri / Noemi Manganaro / Giulia Piccini / Alessandro Manenti / Elisa Pantano / Anna Kabanova / Marco Troisi / Fabiola Vacca / ...Authors: Emanuele Andreano / Emanuele Nicastri / Ida Paciello / Piero Pileri / Noemi Manganaro / Giulia Piccini / Alessandro Manenti / Elisa Pantano / Anna Kabanova / Marco Troisi / Fabiola Vacca / Dario Cardamone / Concetta De Santi / Jonathan L Torres / Gabriel Ozorowski / Linda Benincasa / Hyesun Jang / Cecilia Di Genova / Lorenzo Depau / Jlenia Brunetti / Chiara Agrati / Maria Rosaria Capobianchi / Concetta Castilletti / Arianna Emiliozzi / Massimiliano Fabbiani / Francesca Montagnani / Luisa Bracci / Giuseppe Sautto / Ted M Ross / Emanuele Montomoli / Nigel Temperton / Andrew B Ward / Claudia Sala / Giuseppe Ippolito / Rino Rappuoli /
Abstract: Human monoclonal antibodies are safe, preventive, and therapeutic tools that can be rapidly developed to help restore the massive health and economic disruption caused by the coronavirus disease 2019 ...Human monoclonal antibodies are safe, preventive, and therapeutic tools that can be rapidly developed to help restore the massive health and economic disruption caused by the coronavirus disease 2019 (COVID-19) pandemic. By single-cell sorting 4,277 SARS-CoV-2 spike protein-specific memory B cells from 14 COVID-19 survivors, 453 neutralizing antibodies were identified. The most potent neutralizing antibodies recognized the spike protein receptor-binding domain, followed in potency by antibodies that recognize the S1 domain, the spike protein trimer, and the S2 subunit. Only 1.4% of them neutralized the authentic virus with a potency of 1-10 ng/mL. The most potent monoclonal antibody, engineered to reduce the risk of antibody-dependent enhancement and prolong half-life, neutralized the authentic wild-type virus and emerging variants containing D614G, E484K, and N501Y substitutions. Prophylactic and therapeutic efficacy in the hamster model was observed at 0.25 and 4 mg/kg respectively in absence of Fc functions.
History
DepositionFeb 22, 2021-
Header (metadata) releaseMar 9, 2022-
Map releaseMar 9, 2022-
UpdateMar 9, 2022-
Current statusMar 9, 2022Processing site: RCSB / Status: Released

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Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.0163
  • Imaged by UCSF Chimera
  • Download
  • Surface view colored by cylindrical radius
  • Surface level: 0.0163
  • Imaged by UCSF Chimera
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Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

emd_23523.png

Downloads & links

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Map

FileDownload / File: emd_23523.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationSARS-2 CoV 6P Mut7 in complex with Fab J08
Voxel sizeX=Y=Z: 2.06 Å
Density
Contour LevelBy AUTHOR: 0.0163 / Movie #1: 0.0163
Minimum - Maximum-0.03557263 - 0.08694489
Average (Standard dev.)-8.388052e-05 (±0.003185088)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions256256256
Spacing256256256
CellA=B=C: 527.36 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z2.062.062.06
M x/y/z256256256
origin x/y/z0.0000.0000.000
length x/y/z527.360527.360527.360
α/β/γ90.00090.00090.000
start NX/NY/NZ000
NX/NY/NZ368368368
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS256256256
D min/max/mean-0.0360.087-0.000

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Supplemental data

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Sample components

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Entire : SARS-2 CoV 6P Mut7 Spike Protein in complex with Fab J08

EntireName: SARS-2 CoV 6P Mut7 Spike Protein in complex with Fab J08
Components
  • Complex: SARS-2 CoV 6P Mut7 Spike Protein in complex with Fab J08
    • Complex: fragment antigent binding (Fab) J08
    • Complex: SARS-2 CoV 6P Mut7 Spike Protein

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Supramolecule #1: SARS-2 CoV 6P Mut7 Spike Protein in complex with Fab J08

SupramoleculeName: SARS-2 CoV 6P Mut7 Spike Protein in complex with Fab J08
type: complex / ID: 1 / Parent: 0

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Supramolecule #2: fragment antigent binding (Fab) J08

SupramoleculeName: fragment antigent binding (Fab) J08 / type: complex / ID: 2 / Parent: 1
Source (natural)Organism: Homo sapiens (human)
Recombinant expressionOrganism: Homo sapiens (human)

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Supramolecule #3: SARS-2 CoV 6P Mut7 Spike Protein

SupramoleculeName: SARS-2 CoV 6P Mut7 Spike Protein / type: complex / ID: 3 / Parent: 1
Source (natural)Organism: Severe acute respiratory syndrome coronavirus 2
Recombinant expressionOrganism: Homo sapiens (human)

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Experimental details

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Structure determination

Methodnegative staining
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 7.4
StainingType: NEGATIVE / Material: Uranyl Formate / Details: 2%

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Electron microscopy

MicroscopeFEI TECNAI SPIRIT
Electron beamAcceleration voltage: 120 kV / Electron source: LAB6
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy
Image recordingFilm or detector model: FEI EAGLE (4k x 4k) / Average electron dose: 50.0 e/Å2
Experimental equipment
Model: Tecnai Spirit / Image courtesy: FEI Company

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Image processing

Initial angle assignmentType: OTHER
Final angle assignmentType: OTHER
Final reconstructionResolution.type: BY AUTHOR / Resolution: 29.0 Å / Resolution method: FSC 0.5 CUT-OFF / Number images used: 8229

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