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- EMDB-32870: S protein of Delta variant in complex with ZWD12 focused on RBD_Z... -

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Basic information

Entry
Database: EMDB / ID: EMD-32870
TitleS protein of Delta variant in complex with ZWD12 focused on RBD_ZWD12 sub-complex
Map data
Sample
  • Complex: S protein of Delta variant in complex with ZWD12
    • Complex: S protein of Delta variant
    • Complex: ZWD12
Biological speciesSevere acute respiratory syndrome coronavirus 2 / Homo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.3 Å
AuthorsGuo YY / Zhang YY
Funding support China, 2 items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)32022037 China
National Natural Science Foundation of China (NSFC)81803429 China
CitationJournal: Signal Transduct Target Ther / Year: 2022
Title: Broadly neutralizing antibodies against Omicron-included SARS-CoV-2 variants induced by vaccination.
Authors: Xiangyang Chi / Yingying Guo / Guanying Zhang / Hancong Sun / Jun Zhang / Min Li / Zhengshan Chen / Jin Han / Yuanyuan Zhang / Xinghai Zhang / Pengfei Fan / Zhe Zhang / Busen Wang / Xiaodong ...Authors: Xiangyang Chi / Yingying Guo / Guanying Zhang / Hancong Sun / Jun Zhang / Min Li / Zhengshan Chen / Jin Han / Yuanyuan Zhang / Xinghai Zhang / Pengfei Fan / Zhe Zhang / Busen Wang / Xiaodong Zai / Xuelian Han / Meng Hao / Ting Fang / Jinghan Xu / Shipo Wu / Yi Chen / Yingying Fang / Yunzhu Dong / Bingjie Sun / Jinlong Zhang / Jianmin Li / Guangyu Zhao / Changming Yu / Qiang Zhou / Wei Chen /
Abstract: The SARS-CoV-2 Omicron variant shows substantial resistance to neutralization by infection- and vaccination-induced antibodies, highlighting the demands for research on the continuing discovery of ...The SARS-CoV-2 Omicron variant shows substantial resistance to neutralization by infection- and vaccination-induced antibodies, highlighting the demands for research on the continuing discovery of broadly neutralizing antibodies (bnAbs). Here, we developed a panel of bnAbs against Omicron and other variants of concern (VOCs) elicited by vaccination of adenovirus-vectored COVID-19 vaccine (Ad5-nCoV). We also investigated the human longitudinal antibody responses following vaccination and demonstrated how the bnAbs evolved over time. A monoclonal antibody (mAb), named ZWD12, exhibited potent and broad neutralization against SARS-CoV-2 variants Alpha, Beta, Gamma, Kappa, Delta, and Omicron by blocking the spike protein binding to the angiotensin-converting enzyme 2 (ACE2) and provided complete protection in the challenged prophylactic and therapeutic K18-hACE2 transgenic mouse model. We defined the ZWD12 epitope by determining its structure in complex with the spike (S) protein via cryo-electron microscopy. This study affords the potential to develop broadly therapeutic mAb drugs and suggests that the RBD epitope bound by ZWD12 is a rational target for the design of a broad spectrum of vaccines.
History
DepositionFeb 13, 2022-
Header (metadata) releaseJun 1, 2022-
Map releaseJun 1, 2022-
UpdateJun 1, 2022-
Current statusJun 1, 2022Processing site: PDBj / Status: Released

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Structure visualization

Supplemental images

Downloads & links

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Map

FileDownload / File: emd_32870.map.gz / Format: CCP4 / Size: 91.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.09 Å/pix.
x 288 pix.
= 313.056 Å
1.09 Å/pix.
x 288 pix.
= 313.056 Å
1.09 Å/pix.
x 288 pix.
= 313.056 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.087 Å
Density
Contour LevelBy AUTHOR: 0.035
Minimum - Maximum-0.06301795 - 0.12726754
Average (Standard dev.)8.9200774e-05 (±0.002803658)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions288288288
Spacing288288288
CellA=B=C: 313.056 Å
α=β=γ: 90.0 °

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Supplemental data

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Sample components

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Entire : S protein of Delta variant in complex with ZWD12

EntireName: S protein of Delta variant in complex with ZWD12
Components
  • Complex: S protein of Delta variant in complex with ZWD12
    • Complex: S protein of Delta variant
    • Complex: ZWD12

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Supramolecule #1: S protein of Delta variant in complex with ZWD12

SupramoleculeName: S protein of Delta variant in complex with ZWD12 / type: complex / Chimera: Yes / ID: 1 / Parent: 0 / Macromolecule list: #1-#3

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Supramolecule #2: S protein of Delta variant

SupramoleculeName: S protein of Delta variant / type: complex / Chimera: Yes / ID: 2 / Parent: 1 / Macromolecule list: #1
Source (natural)Organism: Severe acute respiratory syndrome coronavirus 2
Recombinant expressionOrganism: Homo sapiens (human)

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Supramolecule #3: ZWD12

SupramoleculeName: ZWD12 / type: complex / Chimera: Yes / ID: 3 / Parent: 1 / Macromolecule list: #2-#3
Source (natural)Organism: Homo sapiens (human)
Recombinant expressionOrganism: Homo sapiens (human)

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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: 8
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / 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 / Nominal defocus max: 2.2 µm / Nominal defocus min: 1.2 µm
Sample stageSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION (ver. 3.0.6) / Number images used: 159808
Initial angle assignmentType: ANGULAR RECONSTITUTION
Final angle assignmentType: MAXIMUM LIKELIHOOD

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