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Yorodumi- EMDB-37139: Structure of SARS-CoV Spike protein complexed with antibody PW5-5 -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-37139 | |||||||||
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Title | Structure of SARS-CoV Spike protein complexed with antibody PW5-5 | |||||||||
Map data | ||||||||||
Sample |
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Keywords | Antibody / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex | |||||||||
Function / homology | Function and homology information Maturation of spike protein / Translation of Structural Proteins / Virion Assembly and Release / Attachment and Entry / endocytosis involved in viral entry into host cell / SARS-CoV-1 activates/modulates innate immune responses / suppression by virus of host tetherin activity / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / membrane fusion / positive regulation of viral entry into host cell ...Maturation of spike protein / Translation of Structural Proteins / Virion Assembly and Release / Attachment and Entry / endocytosis involved in viral entry into host cell / SARS-CoV-1 activates/modulates innate immune responses / suppression by virus of host tetherin activity / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / membrane fusion / positive regulation of viral entry into host cell / receptor-mediated virion attachment to host cell / 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 / host cell plasma membrane / virion membrane / identical protein binding / membrane Similarity search - Function | |||||||||
Biological species | Severe acute respiratory syndrome coronavirus 2 / Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.87 Å | |||||||||
Authors | Sun L / Mao Q / Wang Y | |||||||||
Funding support | China, 1 items
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Citation | Journal: Cell Discov / Year: 2024 Title: Potent and broadly neutralizing antibodies against sarbecoviruses induced by sequential COVID-19 vaccination. Authors: Xiaoyu Zhao / Tianyi Qiu / Xiner Huang / Qiyu Mao / Yajie Wang / Rui Qiao / Jiayan Li / Tiantian Mao / Yuan Wang / Yewei Cun / Caicui Wang / Cuiting Luo / Chaemin Yoon / Xun Wang / Chen Li / ...Authors: Xiaoyu Zhao / Tianyi Qiu / Xiner Huang / Qiyu Mao / Yajie Wang / Rui Qiao / Jiayan Li / Tiantian Mao / Yuan Wang / Yewei Cun / Caicui Wang / Cuiting Luo / Chaemin Yoon / Xun Wang / Chen Li / Yuchen Cui / Chaoyue Zhao / Minghui Li / Yanjia Chen / Guonan Cai / Wenye Geng / Zixin Hu / Jinglei Cao / Wenhong Zhang / Zhiwei Cao / Hin Chu / Lei Sun / Pengfei Wang / Abstract: The current SARS-CoV-2 variants strikingly evade all authorized monoclonal antibodies and threaten the efficacy of serum-neutralizing activity elicited by vaccination or prior infection, urging the ...The current SARS-CoV-2 variants strikingly evade all authorized monoclonal antibodies and threaten the efficacy of serum-neutralizing activity elicited by vaccination or prior infection, urging the need to develop antivirals against SARS-CoV-2 and related sarbecoviruses. Here, we identified both potent and broadly neutralizing antibodies from a five-dose vaccinated donor who exhibited cross-reactive serum-neutralizing activity against diverse coronaviruses. Through single B-cell sorting and sequencing followed by a tailor-made computational pipeline, we successfully selected 86 antibodies with potential cross-neutralizing ability from 684 antibody sequences. Among them, PW5-570 potently neutralized all SARS-CoV-2 variants that arose prior to Omicron BA.5, and the other three could broadly neutralize all current SARS-CoV-2 variants of concern, SARS-CoV and their related sarbecoviruses (Pangolin-GD, RaTG13, WIV-1, and SHC014). Cryo-EM analysis demonstrates that these antibodies have diverse neutralization mechanisms, such as disassembling spike trimers, or binding to RBM or SD1 to affect ACE2 binding. In addition, prophylactic administration of these antibodies significantly protects nasal turbinate and lung infections against BA.1, XBB.1, and SARS-CoV viral challenge in golden Syrian hamsters, respectively. Importantly, post-exposure treatment with PW5-5 and PW5-535 also markedly protects against XBB.1 challenge in these models. This study reveals the potential utility of computational process to assist screening cross-reactive antibodies, as well as the potency of vaccine-induced broadly neutralizing antibodies against current SARS-CoV-2 variants and related sarbecoviruses, offering promising avenues for the development of broad therapeutic antibody drugs. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_37139.map.gz | 98.1 MB | EMDB map data format | |
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Header (meta data) | emd-37139-v30.xml emd-37139.xml | 18 KB 18 KB | Display Display | EMDB header |
Images | emd_37139.png | 107.7 KB | ||
Filedesc metadata | emd-37139.cif.gz | 6.7 KB | ||
Others | emd_37139_half_map_1.map.gz emd_37139_half_map_2.map.gz | 98.4 MB 98.7 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-37139 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-37139 | HTTPS FTP |
-Validation report
Summary document | emd_37139_validation.pdf.gz | 765.7 KB | Display | EMDB validaton report |
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Full document | emd_37139_full_validation.pdf.gz | 765.2 KB | Display | |
Data in XML | emd_37139_validation.xml.gz | 13.8 KB | Display | |
Data in CIF | emd_37139_validation.cif.gz | 16.1 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-37139 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-37139 | HTTPS FTP |
-Related structure data
Related structure data | 8kdmMC 8kdrC 8kdsC 8kdtC 8kehC 8kejC 8kekC 8keoC 8kepC 8keqC 8kerC 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_37139.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.932 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_37139_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_37139_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : SARS spike protein (S) in complex with broadly neutralizing antib...
Entire | Name: SARS spike protein (S) in complex with broadly neutralizing antibody PW5-5 |
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Components |
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-Supramolecule #1: SARS spike protein (S) in complex with broadly neutralizing antib...
Supramolecule | Name: SARS spike protein (S) in complex with broadly neutralizing antibody PW5-5 type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
-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: 131.982406 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MFIFLLFLTL TSGSDLDRCT TFDDVQAPNY TQHTSSMRGV YYPDEIFRSD TLYLTQDLFL PFYSNVTGFH TINHTFGNPV IPFKDGIYF AATEKSNVVR GWVFGSTMNN KSQSVIIINN STNVVIRACN FELCDNPFFA VSKPMGTQTH TMIFDNAFNC T FEYISDAF ...String: MFIFLLFLTL TSGSDLDRCT TFDDVQAPNY TQHTSSMRGV YYPDEIFRSD TLYLTQDLFL PFYSNVTGFH TINHTFGNPV IPFKDGIYF AATEKSNVVR GWVFGSTMNN KSQSVIIINN STNVVIRACN FELCDNPFFA VSKPMGTQTH TMIFDNAFNC T FEYISDAF SLDVSEKSGN FKHLREFVFK NKDGFLYVYK GYQPIDVVRD LPSGFNTLKP IFKLPLGINI TNFRAILTAF SP AQDIWGT SAAAYFVGYL KPTTFMLKYD ENGTITDAVD CSQNPLAELK CSVKSFEIDK GIYQTSNFRV VPSGDVVRFP NIT NLCPFG EVFNATKFPS VYAWERKKIS NCVADYSVLY NSTFFSTFKC YGVSATKLND LCFSNVYADS FVVKGDDVRQ IAPG QTGVI ADYNYKLPDD FMGCVLAWNT RNIDATSTGN YNYKYRYLRH GKLRPFERDI SNVPFSPDGK PCTPPALNCY WPLND YGFY TTTGIGYQPY RVVVLSFELL NAPATVCGPK LSTDLIKNQC VNFNFNGLTG TGVLTPSSKR FQPFQQFGRD VSDFTD SVR DPKTSEILDI SPCAFGGVSV ITPGTNASSE VAVLYQDVNC TDVSTAIHAD QLTPAWRIYS TGNNVFQTQA GCLIGAE HV DTSYECDIPI GAGICASYHT VSLLRSTSQK SIVAYTMSLG ADSSIAYSNN TIAIPTNFSI SITTEVMPVS MAKTSVDC N MYICGDSTEC ANLLLQYGSF CTQLNRALSG IAAEQDRNTR EVFAQVKQMY KTPTLKYFGG FNFSQILPDP LKPTKRSFI EDLLFNKVTL ADAGFMKQYG ECLGDINARD LICAQKFNGL TVLPPLLTDD MIAAYTAALV SGTATAGWTF GAGAALQIPF AMQMAYRFN GIGVTQNVLY ENQKQIANQF NKAISQIQES LTTTSTALGK LQDVVNQNAQ ALNTLVKQLS SNFGAISSVL N DILSRLDP PEAEVQIDRL ITGRLQSLQT YVTQQLIRAA EIRASANLAA TKMSECVLGQ SKRVDFCGKG YHLMSFPQAA PH GVVFLHV TYVPSQERNF TTAPAICHEG KAYFPREGVF VFNGTSWFIT QRNFFSPQII TTDNTFVSGN CDVVIGIINN TVY DPLQPE LDSFKEELDK YFKNHTSPDV DLGDISGINA SVVNIQKEID RLNEVAKNLN ESLIDLQELG KYEQ UniProtKB: Spike glycoprotein |
-Macromolecule #2: PW5-5 heavy chain
Macromolecule | Name: PW5-5 heavy chain / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 49.374523 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: QVQLVQSGAE VKKPGASVKV SCKTSGYTFT DHYMYWVRQA PGQGLEWMGV INPDAGSVTY AQKFQGRVTM TSDTSTSTVY MELSSLRSE DTAVYYCARD LFFIPAANSF DYWGQGTLVT VSSTKGPSVF PLAPSSKSTS GGTAALGCLV KDYFPEPVTV S WNSGALTS ...String: QVQLVQSGAE VKKPGASVKV SCKTSGYTFT DHYMYWVRQA PGQGLEWMGV INPDAGSVTY AQKFQGRVTM TSDTSTSTVY MELSSLRSE DTAVYYCARD LFFIPAANSF DYWGQGTLVT VSSTKGPSVF PLAPSSKSTS GGTAALGCLV KDYFPEPVTV S WNSGALTS GVHTFPAVLQ SSGLYSLSSV VTVPSSSLGT QTYICNVNHK PSNTKVDKKV EPKSCDKTHT CPPCPAPELL GG PSVFLFP PKPKDTLMIS RTPEVTCVVV DVSHEDPEVK FNWYVDGVEV HNAKTKPREE QYNSTYRVVS VLTVLHQDWL NGK EYKCKV SNKALPAPIE KTISKAKGQP REPQVYTLPP SRDELTKNQV SLTCLVKGFY PSDIAVEWES NGQPENNYKT TPPV LDSDG SFFLYSKLTV DKSRWQQGNV FSCSVLHEAL HSHYTQKSLS LSPGK |
-Macromolecule #3: PW5-5 light chain
Macromolecule | Name: PW5-5 light chain / type: protein_or_peptide / ID: 3 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 23.782463 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: EIVLTQSPAT LSLSPGERAT LSCRASQSVS SYLAWYQQKP GQAPRLLIYD ATNRATGIPA RFSGSGSGTD FTLTISSLEP EDFAVYYCQ HRSNWPRMFT FGQGTKLEIK RTVAAPSVFI FPPSDEQLKS GTASVVCLLN NFYPREAKVQ WKVDNALQSG N SQESVTEQ ...String: EIVLTQSPAT LSLSPGERAT LSCRASQSVS SYLAWYQQKP GQAPRLLIYD ATNRATGIPA RFSGSGSGTD FTLTISSLEP EDFAVYYCQ HRSNWPRMFT FGQGTKLEIK RTVAAPSVFI FPPSDEQLKS GTASVVCLLN NFYPREAKVQ WKVDNALQSG N SQESVTEQ DSKDSTYSLS STLTLSKADY EKHKVYACEV THQGLSSPVT KSFNRGEC |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 8 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.2 µm / Nominal defocus min: 1.2 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: PDB ENTRY PDB model - PDB ID: |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 2.87 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 649448 |
Initial angle assignment | Type: PROJECTION MATCHING |
Final angle assignment | Type: PROJECTION MATCHING |