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- EMDB-14853: SARS-CoV-2 Spike in complex with the neutralizing antibody Cv2.1169 -

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Basic information

Entry
Database: EMDB / ID: EMD-14853
TitleSARS-CoV-2 Spike in complex with the neutralizing antibody Cv2.1169
Map data
Sample
  • Complex: Complex of the trimeric SARS-CoV-2 Spike bound to the Fab fragment from the IgA antibody Cv2.1169
KeywordsSARS-Cov-2 / broad / potent / antibody / IgA / VIRAL PROTEIN
Biological speciesSevere acute respiratory syndrome coronavirus 2
Methodsingle particle reconstruction / cryo EM / Resolution: 2.85 Å
AuthorsGuardado-Calvo P / Fernandez I / Rey FA
Funding support1 items
OrganizationGrant numberCountry
Not funded
CitationJournal: J Exp Med / Year: 2022
Title: Potent human broadly SARS-CoV-2-neutralizing IgA and IgG antibodies effective against Omicron BA.1 and BA.2.
Authors: Cyril Planchais / Ignacio Fernández / Timothée Bruel / Guilherme Dias de Melo / Matthieu Prot / Maxime Beretta / Pablo Guardado-Calvo / Jérémy Dufloo / Luis M Molinos-Albert / Marija ...Authors: Cyril Planchais / Ignacio Fernández / Timothée Bruel / Guilherme Dias de Melo / Matthieu Prot / Maxime Beretta / Pablo Guardado-Calvo / Jérémy Dufloo / Luis M Molinos-Albert / Marija Backovic / Jeanne Chiaravalli / Emilie Giraud / Benjamin Vesin / Laurine Conquet / Ludivine Grzelak / Delphine Planas / Isabelle Staropoli / Florence Guivel-Benhassine / Thierry Hieu / Mikaël Boullé / Minerva Cervantes-Gonzalez / Marie-Noëlle Ungeheuer / Pierre Charneau / Sylvie van der Werf / Fabrice Agou / / / Jordan D Dimitrov / Etienne Simon-Lorière / Hervé Bourhy / Xavier Montagutelli / Félix A Rey / Olivier Schwartz / Hugo Mouquet /
Abstract: Memory B-cell and antibody responses to the SARS-CoV-2 spike protein contribute to long-term immune protection against severe COVID-19, which can also be prevented by antibody-based interventions. ...Memory B-cell and antibody responses to the SARS-CoV-2 spike protein contribute to long-term immune protection against severe COVID-19, which can also be prevented by antibody-based interventions. Here, wide SARS-CoV-2 immunoprofiling in Wuhan COVID-19 convalescents combining serological, cellular, and monoclonal antibody explorations revealed humoral immunity coordination. Detailed characterization of a hundred SARS-CoV-2 spike memory B-cell monoclonal antibodies uncovered diversity in their repertoire and antiviral functions. The latter were influenced by the targeted spike region with strong Fc-dependent effectors to the S2 subunit and potent neutralizers to the receptor-binding domain. Amongst those, Cv2.1169 and Cv2.3194 antibodies cross-neutralized SARS-CoV-2 variants of concern, including Omicron BA.1 and BA.2. Cv2.1169, isolated from a mucosa-derived IgA memory B cell demonstrated potency boost as IgA dimers and therapeutic efficacy as IgG antibodies in animal models. Structural data provided mechanistic clues to Cv2.1169 potency and breadth. Thus, potent broadly neutralizing IgA antibodies elicited in mucosal tissues can stem SARS-CoV-2 infection, and Cv2.1169 and Cv2.3194 are prime candidates for COVID-19 prevention and treatment.
History
DepositionApr 27, 2022-
Header (metadata) releaseMay 18, 2022-
Map releaseMay 18, 2022-
UpdateJun 28, 2023-
Current statusJun 28, 2023Processing site: PDBe / Status: Released

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Structure visualization

Supplemental images

emd_14853.png

Downloads & links

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Map

FileDownload / File: emd_14853.map.gz / Format: CCP4 / Size: 325 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Voxel sizeX=Y=Z: 0.86 Å
Density
Contour LevelBy AUTHOR: 0.207
Minimum - Maximum-2.2937815 - 4.1418786
Average (Standard dev.)0.0005428406 (±0.07902147)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions440440440
Spacing440440440
CellA=B=C: 378.4 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #1

Fileemd_14853_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #2

Fileemd_14853_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : Complex of the trimeric SARS-CoV-2 Spike bound to the Fab fragmen...

EntireName: Complex of the trimeric SARS-CoV-2 Spike bound to the Fab fragment from the IgA antibody Cv2.1169
Components
  • Complex: Complex of the trimeric SARS-CoV-2 Spike bound to the Fab fragment from the IgA antibody Cv2.1169

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Supramolecule #1: Complex of the trimeric SARS-CoV-2 Spike bound to the Fab fragmen...

SupramoleculeName: Complex of the trimeric SARS-CoV-2 Spike bound to the Fab fragment from the IgA antibody Cv2.1169
type: complex / ID: 1 / Parent: 0
Source (natural)Organism: Severe acute respiratory syndrome coronavirus 2

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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

Concentration0.4 mg/mL
BufferpH: 8
GridModel: Quantifoil R1.2/1.3
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 281 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 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: 3.0 µm / Nominal defocus min: 1.0 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.85 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 498560
Initial angle assignmentType: NOT APPLICABLE
Final angle assignmentType: NOT APPLICABLE

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