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- EMDB-43306: cryo-EM structure of a non-neutralizing antibody V3-21 in complex... -

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Basic information

Entry
Database: EMDB / ID: EMD-43306
Titlecryo-EM structure of a non-neutralizing antibody V3-21 in complex with SARS-CoV-2 spike
Map dataunsharpened map
Sample
  • Complex: Fab:spike complex
Keywordsantibody / SARS-CoV-2 / IMMUNE SYSTEM
Biological speciesSevere acute respiratory syndrome coronavirus 2
Methodsingle particle reconstruction / cryo EM / Resolution: 4.31 Å
AuthorsBajic G / Adelsberg DC
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)AI168178 United States
CitationJournal: Cell Rep / Year: 2024
Title: Protective effect and molecular mechanisms of human non-neutralizing cross-reactive spike antibodies elicited by SARS-CoV-2 mRNA vaccination.
Authors: Jordan J Clark / Irene Hoxie / Daniel C Adelsberg / Iden A Sapse / Robert Andreata-Santos / Jeremy S Yong / Fatima Amanat / Johnstone Tcheou / Ariel Raskin / Gagandeep Singh / Irene ...Authors: Jordan J Clark / Irene Hoxie / Daniel C Adelsberg / Iden A Sapse / Robert Andreata-Santos / Jeremy S Yong / Fatima Amanat / Johnstone Tcheou / Ariel Raskin / Gagandeep Singh / Irene González-Domínguez / Julia E Edgar / Stylianos Bournazos / Weina Sun / Juan Manuel Carreño / Viviana Simon / Ali H Ellebedy / Goran Bajic / Florian Krammer /
Abstract: Neutralizing antibodies correlate with protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Recent studies, however, show that binding antibody titers, in the absence of ...Neutralizing antibodies correlate with protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Recent studies, however, show that binding antibody titers, in the absence of robust neutralizing activity, also correlate with protection against disease progression. Non-neutralizing antibodies cannot directly protect against infection but may recruit effector cells and thus contribute to the clearance of infected cells. Additionally, they often bind conserved epitopes across multiple variants. Here, we characterize 42 human monoclonal antibodies (mAbs) from coronavirus disease 2019 (COVID-19)-vaccinated individuals. Most of these antibodies exhibit no neutralizing activity in vitro, but several non-neutralizing antibodies provide protection against lethal challenge with SARS-CoV-2 in different animal models. A subset of those mAbs shows a clear dependence on Fc-mediated effector functions. We have determined the structures of three non-neutralizing antibodies, with two targeting the receptor-binding domain and one that binds the subdomain 1 region. Our data confirm the real-world observation in humans that non-neutralizing antibodies to SARS-CoV-2 can be protective.
History
DepositionJan 8, 2024-
Header (metadata) releaseNov 27, 2024-
Map releaseNov 27, 2024-
UpdateNov 27, 2024-
Current statusNov 27, 2024Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_43306.png

Downloads & links

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Map

FileDownload / File: emd_43306.map.gz / Format: CCP4 / Size: 512 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Annotationunsharpened map
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.83 Å/pix.
x 512 pix.
= 422.4 Å		0.83 Å/pix.
x 512 pix.
= 422.4 Å		0.83 Å/pix.
x 512 pix.
= 422.4 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.825 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.2
Minimum - Maximum-0.3697142 - 1.1957382
Average (Standard dev.)-0.0009834719 (±0.022789506)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions512512512
Spacing512512512
CellA=B=C: 422.4 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: half-map 1

Fileemd_43306_half_map_1.map
Annotationhalf-map 1
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: half-map 2

Fileemd_43306_half_map_2.map
Annotationhalf-map 2
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : Fab:spike complex

EntireName: Fab:spike complex
Components
  • Complex: Fab:spike complex

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Supramolecule #1: Fab:spike complex

SupramoleculeName: Fab:spike complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1
Source (natural)Organism: Severe acute respiratory syndrome coronavirus 2
Molecular weightTheoretical: 500 kDa/nm

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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: 56.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: OTHER / Imaging mode: OTHER / Nominal defocus max: 1.5 µm / Nominal defocus min: 0.5 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Startup modelType of model: OTHER
Final reconstructionResolution.type: BY AUTHOR / Resolution: 4.31 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 40000
Initial angle assignmentType: ANGULAR RECONSTITUTION
Final angle assignmentType: ANGULAR RECONSTITUTION

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