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- EMDB-61825: Structure of SARS-CoV-2 Spike in complex with antibodies 3E2, 9G1... -

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Basic information

Entry
Database: EMDB / ID: EMD-61825
TitleStructure of SARS-CoV-2 Spike in complex with antibodies 3E2, 9G11 and 13H7 (C1)
Map data
Sample
  • Complex: SARS-CoV-2 spike in complex with 3E2, 9G11 and 13H7 Fab
    • Complex: The Fab of 3E2
    • Complex: SARS-CoV-2 spike
    • Complex: The Fab of 9G11
    • Complex: The Fab of 13H7
KeywordsSARS-CoV-2 / RBD / Fab / VIRAL PROTEIN
Biological speciesHomo sapiens (human) / Mus (mice)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.32 Å
AuthorsJiang Y / Sun H / Zheng Q / Li S
Funding support1 items
OrganizationGrant numberCountry
Not funded
CitationJournal: Emerg Microbes Infect / Year: 2024
Title: Structural insight into broadening SARS-CoV-2 neutralization by an antibody cocktail harbouring both NTD and RBD potent antibodies.
Authors: Wenling Jiang / Yanan Jiang / Hui Sun / Tingting Deng / Kunyu Yu / Qianjiao Fang / Huimin Ge / Miaoling Lan / Yanling Lin / Zhongyue Fang / Yali Zhang / Lizhi Zhou / Tingting Li / Hai Yu / ...Authors: Wenling Jiang / Yanan Jiang / Hui Sun / Tingting Deng / Kunyu Yu / Qianjiao Fang / Huimin Ge / Miaoling Lan / Yanling Lin / Zhongyue Fang / Yali Zhang / Lizhi Zhou / Tingting Li / Hai Yu / Qingbing Zheng / Shaowei Li / Ningshao Xia / Ying Gu /
Abstract: The continual emergence of highly pathogenic novel coronaviruses and their variants has underscored the importance of neutralizing monoclonal antibodies (mAbs) as a pivotal therapeutic approach. In ...The continual emergence of highly pathogenic novel coronaviruses and their variants has underscored the importance of neutralizing monoclonal antibodies (mAbs) as a pivotal therapeutic approach. In the present study, we report the specific neutralizing antibodies 13H7 and 9G11, which target the N-terminal domain (NTD) and receptor-binding domain (RBD) of the SARS-CoV-2, respectively. The comparative analysis observed that 13H7 not only neutralizes early variants of concern (VOCs) but also exhibits neutralizing activity against the Omicron sublineage, including BA.4, BA.5, BQ.1, and BQ.1.1. 9G11, as an RBD antibody, also demonstrated remarkable neutralizing efficacy. A cocktail antibody combining 13H7 and 9G11 with the previously reported 3E2 broaden the neutralization spectrum against new variants of the SARS-CoV-2. We elucidated the cryo-EM structure of the complex, clarifying the mechanism of action of the cocktail antibody combination. Additionally, we also emphasized the molecular mechanism between 13H7 and SARS-CoV-2 NTD, revealing the impact of Y144 and H146 residue deletions and mutations on the neutralizing efficacy of 13H7. Taken together, our findings not only offer novel insights into the combination therapy of NTD and RBD neutralizing mAbs but also lay a theoretical foundation for the development of vaccines targeting NTD antibodies, thus providing valuable understanding of alleviating the emergence of SARS-CoV-2 variants.
History
DepositionOct 7, 2024-
Header (metadata) releaseJan 8, 2025-
Map releaseJan 8, 2025-
UpdateJan 8, 2025-
Current statusJan 8, 2025Processing site: PDBc / Status: Released

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Structure visualization

Supplemental images

emd_61825.png

Downloads & links

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Map

FileDownload / File: emd_61825.map.gz / Format: CCP4 / Size: 729 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
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Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.78 Å/pix.
x 576 pix.
= 448.128 Å		0.78 Å/pix.
x 576 pix.
= 448.128 Å		0.78 Å/pix.
x 576 pix.
= 448.128 Å

Surface

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Slices (1/3)

Slices (1/2)

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Images are generated by Spider.

Voxel sizeX=Y=Z: 0.778 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.03
Minimum - Maximum-0.1389424 - 0.3947691
Average (Standard dev.)-0.0002916702 (±0.008968608)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions576576576
Spacing576576576
CellA=B=C: 448.128 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #1

Fileemd_61825_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_61825_half_map_2.map
Projections & Slices
AxesZYX

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Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : SARS-CoV-2 spike in complex with 3E2, 9G11 and 13H7 Fab

EntireName: SARS-CoV-2 spike in complex with 3E2, 9G11 and 13H7 Fab
Components
  • Complex: SARS-CoV-2 spike in complex with 3E2, 9G11 and 13H7 Fab
    • Complex: The Fab of 3E2
    • Complex: SARS-CoV-2 spike
    • Complex: The Fab of 9G11
    • Complex: The Fab of 13H7

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Supramolecule #1: SARS-CoV-2 spike in complex with 3E2, 9G11 and 13H7 Fab

SupramoleculeName: SARS-CoV-2 spike in complex with 3E2, 9G11 and 13H7 Fab
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#5

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Supramolecule #2: The Fab of 3E2

SupramoleculeName: The Fab of 3E2 / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #3, #5

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Supramolecule #3: SARS-CoV-2 spike

SupramoleculeName: SARS-CoV-2 spike / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #4
Source (natural)Organism: Homo sapiens (human)

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Supramolecule #4: The Fab of 9G11

SupramoleculeName: The Fab of 9G11 / type: complex / ID: 4 / Parent: 1
Source (natural)Organism: Mus (mice)

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Supramolecule #5: The Fab of 13H7

SupramoleculeName: The Fab of 13H7 / type: complex / ID: 5 / Parent: 1
Source (natural)Organism: Mus (mice)

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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: 7.4
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TECNAI F30
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 60.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: OTHER
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 5.416 µm / Nominal defocus min: 1.0 µm
Experimental equipment
Model: Tecnai F30 / Image courtesy: FEI Company

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Image processing

Startup modelType of model: OTHER
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.32 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 307127
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD

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