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Yorodumi- EMDB-32497: SARS-CoV-2 spike in complex with the ZB8 neutralizing antibody Fa... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-32497 | |||||||||
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Title | SARS-CoV-2 spike in complex with the ZB8 neutralizing antibody Fab (focused refinement on Fab-RBD) | |||||||||
Map data | Fab-spike | |||||||||
Sample |
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Keywords | 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 / positive regulation of viral entry into host cell / receptor-mediated virion attachment to host cell / receptor ligand activity / symbiont-mediated suppression of host innate immune response / 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 | single particle reconstruction / cryo EM / Resolution: 3.11 Å | |||||||||
Authors | Zeng JW | |||||||||
Funding support | China, 1 items
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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
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_32497.map.gz | 9.5 MB | EMDB map data format | |
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Header (meta data) | emd-32497-v30.xml emd-32497.xml | 14.1 KB 14.1 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_32497_fsc.xml | 12.8 KB | Display | FSC data file |
Images | emd_32497.png | 80.9 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-32497 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-32497 | HTTPS FTP |
-Validation report
Summary document | emd_32497_validation.pdf.gz | 339 KB | Display | EMDB validaton report |
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Full document | emd_32497_full_validation.pdf.gz | 338.6 KB | Display | |
Data in XML | emd_32497_validation.xml.gz | 12.6 KB | Display | |
Data in CIF | emd_32497_validation.cif.gz | 17.2 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-32497 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-32497 | HTTPS FTP |
-Related structure data
Related structure data | 7wh8MC 7whbC 7whdC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_32497.map.gz / Format: CCP4 / Size: 178 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Annotation | Fab-spike | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.0979 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Sample components
-Entire : Fab-Spike
Entire | Name: Fab-Spike |
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Components |
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-Supramolecule #1: Fab-Spike
Supramolecule | Name: Fab-Spike / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Homo sapiens (human) |
-Supramolecule #2: Fab
Supramolecule | Name: Fab / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
-Supramolecule #3: Spike
Supramolecule | Name: Spike / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #3 |
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-Macromolecule #1: antibody ZB8 heavy chain
Macromolecule | Name: antibody ZB8 heavy chain / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 23.465361 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: EVQLVQSGAE VKKPGSSVKV SCKASGGTFS NYGISWVRQA PGQGLEWMGR ILPTFGTANS AQKFQGRVTI TADESTGTAY MELRSLRSE DTAVYYCAKE GLAFLGYGMD VWGQGTTVTV SSASTKGPSV FPLAPSSKST SGGTAALGCL VKDYFPEPVT V SWNSGALT ...String: EVQLVQSGAE VKKPGSSVKV SCKASGGTFS NYGISWVRQA PGQGLEWMGR ILPTFGTANS AQKFQGRVTI TADESTGTAY MELRSLRSE DTAVYYCAKE GLAFLGYGMD VWGQGTTVTV SSASTKGPSV FPLAPSSKST SGGTAALGCL VKDYFPEPVT V SWNSGALT SGVHTFPAVL QSSGLYSLSS VVTVPSSSLG TQTYICNVNH KPSNTKVDKK VEPKSC |
-Macromolecule #2: antibody ZB8 light chain
Macromolecule | Name: antibody ZB8 light chain / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 23.346963 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: EIVLTQSPGT LSLSPGERAT LSCRASQSVS SYLAWYQQKP GQAPRLLIYD ASNRATGIPA RFIGSGSGTD FTLTISSLEP EDFAVYFCQ QRSNWPLTFG GGTKVEIKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS Q ESVTEQDS ...String: EIVLTQSPGT LSLSPGERAT LSCRASQSVS SYLAWYQQKP GQAPRLLIYD ASNRATGIPA RFIGSGSGTD FTLTISSLEP EDFAVYFCQ QRSNWPLTFG GGTKVEIKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS Q ESVTEQDS KDSTYSLSST LTLSKADYEK HKVYACEVTH QGLSSPVTKS FNRGEC |
-Macromolecule #3: Spike glycoprotein
Macromolecule | Name: Spike glycoprotein / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
Molecular weight | Theoretical: 31.059883 KDa |
Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
Sequence | String: NFRVQPTESI VRFPNITNLC PFGEVFNATR FASVYAWNRK RISNCVADYS VLYNSASFST FKCYGVSPTK LNDLCFTNVY ADSFVIRGD EVRQIAPGQT GKIADYNYKL PDDFTGCVIA WNSNNLDSKV GGNYNYLYRL FRKSNLKPFE RDISTEIYQA G STPCNGVE ...String: NFRVQPTESI VRFPNITNLC PFGEVFNATR FASVYAWNRK RISNCVADYS VLYNSASFST FKCYGVSPTK LNDLCFTNVY ADSFVIRGD EVRQIAPGQT GKIADYNYKL PDDFTGCVIA WNSNNLDSKV GGNYNYLYRL FRKSNLKPFE RDISTEIYQA G STPCNGVE GFNCYFPLQS YGFQPTNGVG YQPYRVVVLS FELLHAPATV CGPKKSTNLV KNKCVNFNFN GLTGTGVLTE SN KKFLPFQ QFGRDIADTT DAVRDPQTLE ILDITPCSFG UniProtKB: Spike glycoprotein |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: OTHER / Imaging mode: OTHER / Nominal defocus max: 3.0 µm / Nominal defocus min: 1.0 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |