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- EMDB-33051: Cryo-EM structure of SARS-CoV spike protein in complex with three... -

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Entry
Database: EMDB / ID: EMD-33051
TitleCryo-EM structure of SARS-CoV spike protein in complex with three nAbs X01, X10 and X17
Map data
Sample
  • Complex: Cryo-EM structure of SARS-CoV-2 spike protein in complex with three nAbs X01, X10 and X17
    • Complex: SARS-CoV-2 spike proteinCoronavirus spike protein
    • Complex: nAbs X01, X10 and X17
Biological speciesSevere acute respiratory syndrome coronavirus 2 / Mus musculus (house mouse)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.74 Å
AuthorsSun H / Liu L / Zhang T / Zheng Q / Li S / Xia N
Funding support1 items
OrganizationGrant numberCountry
Not funded
CitationJournal: Proc Natl Acad Sci U S A / Year: 2022
Title: The neutralizing breadth of antibodies targeting diverse conserved epitopes between SARS-CoV and SARS-CoV-2.
Authors: Hualong Xiong / Hui Sun / Siling Wang / Lunzhi Yuan / Liqin Liu / Yuhe Zhu / Jinlei Zhang / Yang Huang / Ruoyao Qi / Yao Jiang / Jian Ma / Ming Zhou / Yue Ma / Rao Fu / Siping Yan / Mingxi ...Authors: Hualong Xiong / Hui Sun / Siling Wang / Lunzhi Yuan / Liqin Liu / Yuhe Zhu / Jinlei Zhang / Yang Huang / Ruoyao Qi / Yao Jiang / Jian Ma / Ming Zhou / Yue Ma / Rao Fu / Siping Yan / Mingxi Yue / Yangtao Wu / Min Wei / Yizhen Wang / Tingting Li / Yingbin Wang / Zizheng Zheng / Hai Yu / Tong Cheng / Shaowei Li / Quan Yuan / Jun Zhang / Yi Guan / Qingbing Zheng / Tianying Zhang / Ningshao Xia /
Abstract: Antibody therapeutics for the treatment of COVID-19 have been highly successful. However, the recent emergence of the Omicron variant has posed a challenge, as it evades detection by most existing ...Antibody therapeutics for the treatment of COVID-19 have been highly successful. However, the recent emergence of the Omicron variant has posed a challenge, as it evades detection by most existing SARS-CoV-2 neutralizing antibodies (nAbs). Here, we successfully generated a panel of SARS-CoV-2/SARS-CoV cross-neutralizing antibodies by sequential immunization of the two pseudoviruses. Of the potential candidates, we found that nAbs X01, X10, and X17 offer broad neutralizing potential against most variants of concern, with X17 further identified as a Class 5 nAb with undiminished neutralization against the Omicron variant. Cryo-electron microscopy structures of the three antibodies together in complex with each of the spike proteins of the prototypical SARS-CoV, SARS-CoV-2, and Delta and Omicron variants of SARS-CoV-2 defined three nonoverlapping conserved epitopes on the receptor-binding domain. The triple-antibody mixture exhibited enhanced resistance to viral evasion and effective protection against infection of the Beta variant in hamsters. Our findings will aid the development of antibody therapeutics and broad vaccines against SARS-CoV-2 and its emerging variants.
History
DepositionMar 10, 2022-
Header (metadata) releaseAug 17, 2022-
Map releaseAug 17, 2022-
UpdateNov 23, 2022-
Current statusNov 23, 2022Processing site: PDBj / Status: Released

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Structure visualization

Supplemental images

Downloads & links

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Map

FileDownload / File: emd_33051.map.gz / Format: CCP4 / Size: 729 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Voxel sizeX=Y=Z: 0.778 Å
Density
Contour LevelBy AUTHOR: 0.03
Minimum - Maximum-0.082151614 - 0.24655287
Average (Standard dev.)-9.088525e-05 (±0.007028514)
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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Sample components

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Entire : Cryo-EM structure of SARS-CoV-2 spike protein in complex with thr...

EntireName: Cryo-EM structure of SARS-CoV-2 spike protein in complex with three nAbs X01, X10 and X17
Components
  • Complex: Cryo-EM structure of SARS-CoV-2 spike protein in complex with three nAbs X01, X10 and X17
    • Complex: SARS-CoV-2 spike proteinCoronavirus spike protein
    • Complex: nAbs X01, X10 and X17

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Supramolecule #1: Cryo-EM structure of SARS-CoV-2 spike protein in complex with thr...

SupramoleculeName: Cryo-EM structure of SARS-CoV-2 spike protein in complex with three nAbs X01, X10 and X17
type: complex / Chimera: Yes / ID: 1 / Parent: 0 / Macromolecule list: #1-#7

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Supramolecule #2: SARS-CoV-2 spike protein

SupramoleculeName: SARS-CoV-2 spike protein / type: complex / Chimera: Yes / ID: 2 / Parent: 1 / Macromolecule list: #1
Source (natural)Organism: Severe acute respiratory syndrome coronavirus 2

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Supramolecule #3: nAbs X01, X10 and X17

SupramoleculeName: nAbs X01, X10 and X17 / type: complex / Chimera: Yes / ID: 3 / Parent: 1 / Macromolecule list: #2-#7
Source (natural)Organism: Mus musculus (house mouse)

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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
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.8 µm
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 60.0 e/Å2
Experimental equipment
Model: Tecnai F30 / Image courtesy: FEI Company

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Image processing

Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.74 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 230838

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