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Yorodumi- EMDB-32498: SARS-CoV-2 spike in complex with the ZB8 neutralizing antibody Fa... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-32498 | |||||||||
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Title | SARS-CoV-2 spike in complex with the ZB8 neutralizing antibody Fab (3U) | |||||||||
Map data | Spike-3Fabs | |||||||||
Sample |
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Keywords | SARS-CoV-2 spike / receptor binding domain / antibody / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM 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 / membrane fusion / Attachment and Entry / 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 | Severe acute respiratory syndrome coronavirus 2 / Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.67 Å | |||||||||
Authors | Zeng JW / Ge 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_32498.map.gz | 9.1 MB | EMDB map data format | |
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Header (meta data) | emd-32498-v30.xml emd-32498.xml | 15.3 KB 15.3 KB | Display Display | EMDB header |
Images | emd_32498.png | 91.8 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-32498 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-32498 | HTTPS FTP |
-Validation report
Summary document | emd_32498_validation.pdf.gz | 382.2 KB | Display | EMDB validaton report |
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Full document | emd_32498_full_validation.pdf.gz | 381.9 KB | Display | |
Data in XML | emd_32498_validation.xml.gz | 6.7 KB | Display | |
Data in CIF | emd_32498_validation.cif.gz | 7.7 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-32498 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-32498 | HTTPS FTP |
-Related structure data
Related structure data | 7whbMC 7wh8C 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_32498.map.gz / Format: CCP4 / Size: 178 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Annotation | Spike-3Fabs | ||||||||||||||||||||
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: #1-#3 |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
-Supramolecule #2: Spike
Supramolecule | Name: Spike / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: Homo sapiens (human) |
-Supramolecule #3: Fab
Supramolecule | Name: Fab / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2-#3 |
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-Macromolecule #1: Spike glycoprotein
Macromolecule | Name: Spike glycoprotein / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
Molecular weight | Theoretical: 124.037398 KDa |
Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
Sequence | String: AYTNSFTRGV YYPDKVFRSS VLHSTQDLFL PFFSNVTWFH AIHVSGTNGT KRFDNPVLPF NDGVYFASTE KSNIIRGWIF GTTLDSKTQ SLLIVNNATN VVIKVCEFQF CNDPFLGVYY HKNNKSWMES EFRVYSSANN CTFEYVSQPF LMDLEGKQGN F KNLREFVF ...String: AYTNSFTRGV YYPDKVFRSS VLHSTQDLFL PFFSNVTWFH AIHVSGTNGT KRFDNPVLPF NDGVYFASTE KSNIIRGWIF GTTLDSKTQ SLLIVNNATN VVIKVCEFQF CNDPFLGVYY HKNNKSWMES EFRVYSSANN CTFEYVSQPF LMDLEGKQGN F KNLREFVF KNIDGYFKIY SKHTPINLVR DLPQGFSALE PLVDLPIGIN ITRFQTLLAL HRSYLTPGDS SSGWTAGAAA YY VGYLQPR TFLLKYNENG TITDAVDCAL DPLSETKCTL KSFTVEKGIY QTSNFRVQPT ESIVRFPNIT NLCPFGEVFN ATR FASVYA WNRKRISNCV ADYSVLYNSA SFSTFKCYGV SPTKLNDLCF TNVYADSFVI RGDEVRQIAP GQTGKIADYN YKLP DDFTG CVIAWNSNNL DSKVGGNYNY LYRLFRKSNL KPFERDISTE IYQAGSTPCN GVEGFNCYFP LQSYGFQPTN GVGYQ PYRV VVLSFELLHA PATVCGPKKS TNLVKNKCVN FNFNGLTGTG VLTESNKKFL PFQQFGRDIA DTTDAVRDPQ TLEILD ITP CSFGGVSVIT PGTNTSNQVA VLYQDVNCTE VPVAIHADQL TPTWRVYSTG SNVFQTRAGC LIGAEHVNNS YECDIPI GA GICASYQTQT NSPRRARSVA SQSIIAYTMS LGAENSVAYS NNSIAIPTNF TISVTTEILP VSMTKTSVDC TMYICGDS T ECSNLLLQYG SFCTQLNRAL TGIAVEQDKN TQEVFAQVKQ IYKTPPIKDF GGFNFSQILP DPSKPSKRSF IEDLLFNKV TLADAGFIKQ YGDCLGDIAA RDLICAQKFN GLTVLPPLLT DEMIAQYTSA LLAGTITSGW TFGAGAALQI PFAMQMAYRF NGIGVTQNV LYENQKLIAN QFNSAIGKIQ DSLSSTASAL GKLQDVVNQN AQALNTLVKQ LSSNFGAISS VLNDILSRLD P PEAEVQID RLITGRLQSL QTYVTQQLIR AAEIRASANL AATKMSECVL GQSKRVDFCG KGYHLMSFPQ SAPHGVVFLH VT YVPAQEK NFTTAPAICH DGKAHFPREG VFVSNGTHWF VTQRNFYEPQ IITTDNTFVS GNCDVVIGIV NNTVYDPLQP ELD UniProtKB: Spike glycoprotein |
-Macromolecule #2: antibody ZB8 heavy chain
Macromolecule | Name: antibody ZB8 heavy chain / type: protein_or_peptide / ID: 2 / Number of copies: 3 / 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 #3: antibody ZB8 light chain
Macromolecule | Name: antibody ZB8 light chain / type: protein_or_peptide / ID: 3 / Number of copies: 3 / 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 #5: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 5 / Number of copies: 18 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ChemComp-NAG: |
-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 |
-Image processing
Startup model | Type of model: INSILICO MODEL |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 2.67 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 351095 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |