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- EMDB-33195: The Cryo-EM structure of SARS-CoV-2 Omicron 3-RBD up spike protei... -

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Entry
Database: EMDB / ID: EMD-33195
TitleThe Cryo-EM structure of SARS-CoV-2 Omicron 3-RBD up spike protein complexed with ZCB11 fab
Map data
Sample
  • Complex: The complex of ZCB11 against Fab SARS-CoV-2 Omicron Spike
    • Complex: The ZCB11 fab
    • Complex: The spike protein of SARS-CoV-2 Omicron variant
Biological speciesHomo sapiens (human) / Severe acute respiratory syndrome coronavirus 2
Methodsingle particle reconstruction / cryo EM / Resolution: 3.56 Å
AuthorsHang L / Dang S
Funding support Hong Kong, 1 items
OrganizationGrant numberCountry
The University Grants Committee, Research Grants Council (RGC) Hong Kong
CitationJournal: Nat Commun / Year: 2022
Title: A broadly neutralizing antibody protects Syrian hamsters against SARS-CoV-2 Omicron challenge.
Authors: Biao Zhou / Runhong Zhou / Bingjie Tang / Jasper Fuk-Woo Chan / Mengxiao Luo / Qiaoli Peng / Shuofeng Yuan / Hang Liu / Bobo Wing-Yee Mok / Bohao Chen / Pui Wang / Vincent Kwok-Man Poon / ...Authors: Biao Zhou / Runhong Zhou / Bingjie Tang / Jasper Fuk-Woo Chan / Mengxiao Luo / Qiaoli Peng / Shuofeng Yuan / Hang Liu / Bobo Wing-Yee Mok / Bohao Chen / Pui Wang / Vincent Kwok-Man Poon / Hin Chu / Chris Chung-Sing Chan / Jessica Oi-Ling Tsang / Chris Chun-Yiu Chan / Ka-Kit Au / Hiu-On Man / Lu Lu / Kelvin Kai-Wang To / Honglin Chen / Kwok-Yung Yuen / Shangyu Dang / Zhiwei Chen /
Abstract: The strikingly high transmissibility and antibody evasion of SARS-CoV-2 Omicron variants have posed great challenges to the efficacy of current vaccines and antibody immunotherapy. Here, we screen 34 ...The strikingly high transmissibility and antibody evasion of SARS-CoV-2 Omicron variants have posed great challenges to the efficacy of current vaccines and antibody immunotherapy. Here, we screen 34 BNT162b2-vaccinees and isolate a public broadly neutralizing antibody ZCB11 derived from the IGHV1-58 family. ZCB11 targets viral receptor-binding domain specifically and neutralizes all SARS-CoV-2 variants of concern, especially with great potency against authentic Omicron and Delta variants. Pseudovirus-based mapping of 57 naturally occurred spike mutations or deletions reveals that S371L results in 11-fold neutralization resistance, but it is rescued by compensating mutations in Omicron variants. Cryo-EM analysis demonstrates that ZCB11 heavy chain predominantly interacts with Omicron spike trimer with receptor-binding domain in up conformation blocking ACE2 binding. In addition, prophylactic or therapeutic ZCB11 administration protects lung infection against Omicron viral challenge in golden Syrian hamsters. These results suggest that vaccine-induced ZCB11 is a promising broadly neutralizing antibody for biomedical interventions against pandemic SARS-CoV-2.
History
DepositionApr 8, 2022-
Header (metadata) releaseJun 29, 2022-
Map releaseJun 29, 2022-
UpdateJul 13, 2022-
Current statusJul 13, 2022Processing site: PDBj / Status: Released

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Structure visualization

Supplemental images

emd_33195.png

Downloads & links

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Map

FileDownload / File: emd_33195.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Voxel sizeX=Y=Z: 1.06 Å
Density
Contour LevelBy AUTHOR: 0.2
Minimum - Maximum-0.22320174 - 0.9757895
Average (Standard dev.)0.0021565394 (±0.04442496)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions320320320
Spacing320320320
CellA=B=C: 339.19998 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #1

Fileemd_33195_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
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Histogram

Histogram (log scale)

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Half map: #2

Fileemd_33195_half_map_2.map
Projections & Slices
AxesZYX

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Sample components

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Entire : The complex of ZCB11 against Fab SARS-CoV-2 Omicron Spike

EntireName: The complex of ZCB11 against Fab SARS-CoV-2 Omicron Spike
Components
  • Complex: The complex of ZCB11 against Fab SARS-CoV-2 Omicron Spike
    • Complex: The ZCB11 fab
    • Complex: The spike protein of SARS-CoV-2 Omicron variant

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Supramolecule #1: The complex of ZCB11 against Fab SARS-CoV-2 Omicron Spike

SupramoleculeName: The complex of ZCB11 against Fab SARS-CoV-2 Omicron Spike
type: complex / Chimera: Yes / ID: 1 / Parent: 0 / Macromolecule list: #1-#3
Details: the formation of Spike-Fab complex, the Omicron Spike trimer (2.2mg/ml) was mixed with Fab (2.9mg/ml) in 1x PBS buffer at a molar ratio of 1:1.2 (Spike monomer:Fab) and incubated on ice for 40 minutes.
Source (natural)Organism: Homo sapiens (human)
Recombinant expressionOrganism: Homo sapiens (human)

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Supramolecule #2: The ZCB11 fab

SupramoleculeName: The ZCB11 fab / type: complex / Chimera: Yes / ID: 2 / Parent: 1 / Macromolecule list: #2-#3
Source (natural)Organism: Severe acute respiratory syndrome coronavirus 2
Recombinant expressionOrganism: Homo sapiens (human)

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Supramolecule #3: The spike protein of SARS-CoV-2 Omicron variant

SupramoleculeName: The spike protein of SARS-CoV-2 Omicron variant / type: complex / Chimera: Yes / ID: 3 / Parent: 1 / Macromolecule list: #1

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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 / Chamber humidity: 100 %

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average exposure time: 4.5 sec. / Average electron dose: 50.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.0 µm / Nominal magnification: 81000
Sample stageCooling holder cryogen: NITROGEN
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

CTF correctionSoftware - Name: cryoSPARC (ver. 2.15)
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.56 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC (ver. 2.15) / Number images used: 86891
Initial angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC (ver. 2.15)
Final angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC (ver. 2.15)

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