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Yorodumi- PDB-7wh8: SARS-CoV-2 spike in complex with the ZB8 neutralizing antibody Fa... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7wh8 | ||||||
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Title | SARS-CoV-2 spike in complex with the ZB8 neutralizing antibody Fab (focused refinement on Fab-RBD) | ||||||
Components |
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Keywords | IMMUNE SYSTEM/VIRAL PROTEIN / SARS-CoV-2 spike / receptor binding domain / antibody / VIRAL PROTEIN / IMMUNE SYSTEM-VIRAL PROTEIN complex | ||||||
Function / homology | Function and homology information Maturation of spike protein / viral translation / Translation of Structural Proteins / Virion Assembly and Release / host cell surface / host extracellular space / suppression by virus of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion / entry receptor-mediated virion attachment to host cell ...Maturation of spike protein / viral translation / Translation of Structural Proteins / Virion Assembly and Release / host cell surface / host extracellular space / suppression by virus of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion / entry receptor-mediated virion attachment to host cell / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / receptor-mediated endocytosis of virus by host cell / Attachment and Entry / membrane fusion / symbiont-mediated suppression of host innate immune response / positive regulation of viral entry into host cell / receptor-mediated virion attachment to host cell / receptor ligand activity / host cell surface receptor binding / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / SARS-CoV-2 activates/modulates innate and adaptive immune responses / host cell plasma membrane / virion membrane / identical protein binding / membrane / plasma membrane Similarity search - Function | ||||||
Biological species | Homo sapiens (human) Severe acute respiratory syndrome coronavirus 2 | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.11 Å | ||||||
Authors | Zeng, J.W. | ||||||
Funding support | China, 1items
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Citation | Journal: Emerg Microbes Infect / Year: 2023 Title: SARS-CoV-2 hijacks neutralizing dimeric IgA for nasal infection and injury in Syrian hamsters. Authors: Biao Zhou / Runhong Zhou / Jasper Fuk-Woo Chan / Jianwei Zeng / Qi Zhang / Shuofeng Yuan / Li Liu / Rémy Robinot / Sisi Shan / Na Liu / Jiwan Ge / Hugo Yat-Hei Kwong / Dongyan Zhou / Haoran ...Authors: Biao Zhou / Runhong Zhou / Jasper Fuk-Woo Chan / Jianwei Zeng / Qi Zhang / Shuofeng Yuan / Li Liu / Rémy Robinot / Sisi Shan / Na Liu / Jiwan Ge / Hugo Yat-Hei Kwong / Dongyan Zhou / Haoran Xu / Chris Chung-Sing Chan / Vincent Kwok-Man Poon / Hin Chu / Ming Yue / Ka-Yi Kwan / Chun-Yin Chan / Chris Chun-Yiu Chan / Kenn Ka-Heng Chik / Zhenglong Du / Ka-Kit Au / Haode Huang / Hiu-On Man / Jianli Cao / Cun Li / Ziyi Wang / Jie Zhou / Youqiang Song / Man-Lung Yeung / Kelvin Kai-Wang To / David D Ho / Lisa A Chakrabarti / Xinquan Wang / Linqi Zhang / Kwok-Yung Yuen / Zhiwei Chen / Abstract: Prevention of robust severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in nasal turbinate (NT) requires evaluation of IgA neutralizing antibodies. Here, we report the efficacy ...Prevention of robust severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in nasal turbinate (NT) requires evaluation of IgA neutralizing antibodies. Here, we report the efficacy of receptor binding domain (RBD)-specific monomeric B8-mIgA1 and B8-mIgA2, and dimeric B8-dIgA1, B8-dIgA2 and TH335-dIgA1 against intranasal SARS-CoV-2 challenge in Syrian hamsters. These antibodies exhibited comparable neutralization potency against authentic virus by competing with human angiotensin converting enzyme-2 (ACE2) receptor for RBD binding. While reducing viral loads in lungs significantly, prophylactic intranasal B8-dIgA unexpectedly led to high amount of infectious viruses and extended damage in NT compared to controls. Mechanistically, B8-dIgA failed to inhibit SARS-CoV-2 cell-to-cell transmission, but was hijacked by the virus through dendritic cell-mediated trans-infection of NT epithelia leading to robust nasal infection. Cryo-EM further revealed B8 as a class II antibody binding trimeric RBDs in 3-up or 2-up/1-down conformation. Neutralizing dIgA, therefore, may engage an unexpected mode of SARS-CoV-2 nasal infection and injury. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7wh8.cif.gz | 134.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7wh8.ent.gz | 103.3 KB | Display | PDB format |
PDBx/mmJSON format | 7wh8.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/wh/7wh8 ftp://data.pdbj.org/pub/pdb/validation_reports/wh/7wh8 | HTTPS FTP |
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-Related structure data
Related structure data | 32497MC 7whbC 7whdC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Antibody | Mass: 23465.361 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell line: HEK293 / Production host: Homo sapiens (human) |
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#2: Antibody | Mass: 23346.963 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): HEK293 / Production host: Homo sapiens (human) |
#3: Protein | Mass: 31059.883 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Severe acute respiratory syndrome coronavirus 2 Gene: S, 2 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: P0DTC2 |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
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Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 7.4 | ||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: OTHER |
Electron lens | Mode: OTHER / Nominal defocus max: 3000 nm / Nominal defocus min: 1000 nm |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-Processing
Software | Name: PHENIX / Version: dev_3965: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.11 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 508653 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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