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Yorodumi- EMDB-43255: Protective effect of human non-neutralizing cross-reactive spike ... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-43255 | |||||||||
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Title | Protective effect of human non-neutralizing cross-reactive spike antibodies elicited by SARS-CoV-2 mRNA vaccination | |||||||||
Map data | focused, deepEMhancer sharpened map | |||||||||
Sample |
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Keywords | antibody / SARS-CoV-2 / spike / IMMUNE SYSTEM | |||||||||
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 / membrane fusion / receptor-mediated endocytosis of virus by host cell / 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 / symbiont-mediated suppression of host innate immune response / 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: 3.6 Å | |||||||||
Authors | Bajic G | |||||||||
Funding support | United States, 1 items
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Citation | Journal: bioRxiv / Year: 2024 Title: Protective effect and molecular mechanisms of human non-neutralizing cross-reactive spike antibodies elicited by SARS-CoV-2 mRNA vaccination. Authors: Jordan Clark / Irene Hoxie / Daniel C Adelsberg / Iden A Sapse / Robert Andreata-Santos / Jeremy S Yong / Fatima Amanat / Johnstone Tcheou / Ariel Raskin / Gagandeep Singh / Irene González- ...Authors: Jordan Clark / Irene Hoxie / Daniel C Adelsberg / Iden A Sapse / Robert Andreata-Santos / Jeremy S Yong / Fatima Amanat / Johnstone Tcheou / Ariel Raskin / Gagandeep Singh / Irene González-Domínguez / Julia E Edgar / Stylianos Bournazos / Weina Sun / Juan Manuel Carreño / Viviana Simon / Ali H Ellebedy / Goran Bajic / Florian Krammer / Abstract: Neutralizing antibodies correlate with protection against SARS-CoV-2. Recent studies, however, show that binding antibody titers, in the absence of robust neutralizing activity, also correlate with ...Neutralizing antibodies correlate with protection against SARS-CoV-2. Recent studies, however, show that binding antibody titers, in the absence of robust neutralizing activity, also correlate with protection from disease progression. Non-neutralizing antibodies cannot directly protect from infection but may recruit effector cells thus contribute to the clearance of infected cells. Also, they often bind conserved epitopes across multiple variants. We characterized 42 human mAbs from COVID-19 vaccinated individuals. Most of these antibodies exhibited no neutralizing activity but several non-neutralizing antibodies protected against lethal challenge with SARS-CoV-2 in different animal models. A subset of those mAbs showed a clear dependence on Fc-mediated effector functions. We determined the structures of three non-neutralizing antibodies with two targeting the RBD, and one that targeting the SD1 region. Our data confirms the real-world observation in humans that non-neutralizing antibodies to SARS-CoV-2 can be protective. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_43255.map.gz | 455.5 MB | EMDB map data format | |
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Header (meta data) | emd-43255-v30.xml emd-43255.xml | 22.8 KB 22.8 KB | Display Display | EMDB header |
Images | emd_43255.png | 93.3 KB | ||
Filedesc metadata | emd-43255.cif.gz | 6.8 KB | ||
Others | emd_43255_additional_1.map.gz emd_43255_additional_2.map.gz emd_43255_half_map_1.map.gz emd_43255_half_map_2.map.gz | 255.9 MB 483.5 MB 475.3 MB 475.3 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-43255 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-43255 | HTTPS FTP |
-Validation report
Summary document | emd_43255_validation.pdf.gz | 761.6 KB | Display | EMDB validaton report |
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Full document | emd_43255_full_validation.pdf.gz | 761.1 KB | Display | |
Data in XML | emd_43255_validation.xml.gz | 18.6 KB | Display | |
Data in CIF | emd_43255_validation.cif.gz | 22.4 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-43255 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-43255 | HTTPS FTP |
-Related structure data
Related structure data | 8viaMC 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_43255.map.gz / Format: CCP4 / Size: 512 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Annotation | focused, deepEMhancer sharpened map | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.069 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Additional map: focused, unsharpened map
File | emd_43255_additional_1.map | ||||||||||||
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Annotation | focused, unsharpened map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: focused, cryoSPARC sharpened map
File | emd_43255_additional_2.map | ||||||||||||
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Annotation | focused, cryoSPARC sharpened map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: half-map 1
File | emd_43255_half_map_1.map | ||||||||||||
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Annotation | half-map 1 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: half-map 2
File | emd_43255_half_map_2.map | ||||||||||||
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Annotation | half-map 2 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : SARS-CoV-2 spike in complex with PVI.V5-4 Fab
Entire | Name: SARS-CoV-2 spike in complex with PVI.V5-4 Fab |
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Components |
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-Supramolecule #1: SARS-CoV-2 spike in complex with PVI.V5-4 Fab
Supramolecule | Name: SARS-CoV-2 spike in complex with PVI.V5-4 Fab / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4 |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 500 kDa/nm |
-Macromolecule #1: Spike protein S1
Macromolecule | Name: Spike protein S1 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
Molecular weight | Theoretical: 74.113141 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: CVNLTTRTQL PPAYTNSFTR GVYYPDKVFR SSVLHSTQDL FLPFFSNVTW FHAIHVSGTN GTKRFDNPVL PFNDGVYFAS TEKSNIIRG WIFGTTLDSK TQSLLIVNNA TNVVIKVCEF QFCNDPFLGV YYHKNNKSWM ESEFRVYSSA NNCTFEYVSQ P FLMDLEGK ...String: CVNLTTRTQL PPAYTNSFTR GVYYPDKVFR SSVLHSTQDL FLPFFSNVTW FHAIHVSGTN GTKRFDNPVL PFNDGVYFAS TEKSNIIRG WIFGTTLDSK TQSLLIVNNA TNVVIKVCEF QFCNDPFLGV YYHKNNKSWM ESEFRVYSSA NNCTFEYVSQ P FLMDLEGK QGNFKNLREF VFKNIDGYFK IYSKHTPINL VRDLPQGFSA LEPLVDLPIG INITRFQTLL ALHRSYLTPG DS SSGWTAG AAAYYVGYLQ PRTFLLKYNE NGTITDAVDC ALDPLSETKC TLKSFTVEKG IYQTSNFRVQ PTESIVRFPN ITN LCPFGE VFNATRFASV YAWNRKRISN CVADYSVLYN SASFSTFKCY GVSPTKLNDL CFTNVYADSF VIRGDEVRQI APGQ TGKIA DYNYKLPDDF TGCVIAWNSN NLDSKVGGNY NYLYRLFRKS NLKPFERDIS TEIYQAGSTP CNGVEGFNCY FPLQS YGFQ PTNGVGYQPY RVVVLSFELL HAPATVCGPK KSTNLVKNKC VNFNFNGLTG TGVLTESNKK FLPFQQFGRD IADTTD AVR DPQTLEILDI TPCSFGGVSV ITPGTNTSNQ VAVLYQDVNC TEVPVAIHAD QLTPTWRVYS TGSNVFQTRA GCLIGAE HV NNSYECDIPI GAGICASYQT UniProtKB: Spike glycoprotein |
-Macromolecule #2: Spike protein S2
Macromolecule | Name: Spike protein S2 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
Molecular weight | Theoretical: 62.353125 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: QTNSPGSASS VASQSIIAYT MSLGAENSVA YSNNSIAIPT NFTISVTTEI LPVSMTKTSV DCTMYICGDS TECSNLLLQY GSFCTQLNR ALTGIAVEQD KNTQEVFAQV KQIYKTPPIK DFGGFNFSQI LPDPSKPSKR SPIEDLLFNK VTLADAGFIK Q YGDCLGDI ...String: QTNSPGSASS VASQSIIAYT MSLGAENSVA YSNNSIAIPT NFTISVTTEI LPVSMTKTSV DCTMYICGDS TECSNLLLQY GSFCTQLNR ALTGIAVEQD KNTQEVFAQV KQIYKTPPIK DFGGFNFSQI LPDPSKPSKR SPIEDLLFNK VTLADAGFIK Q YGDCLGDI AARDLICAQK FNGLTVLPPL LTDEMIAQYT SALLAGTITS GWTFGAGPAL QIPFPMQMAY RFNGIGVTQN VL YENQKLI ANQFNSAIGK IQDSLSSTPS ALGKLQDVVN QNAQALNTLV KQLSSNFGAI SSVLNDILSR LDPPEAEVQI DRL ITGRLQ SLQTYVTQQL IRAAEIRASA NLAATKMSEC VLGQSKRVDF CGKGYHLMSF PQSAPHGVVF LHVTYVPAQE KNFT TAPAI CHDGKAHFPR EGVFVSNGTH WFVTQRNFYE PQIITTDNTF VSGNCDVVIG IVNNTVYDPL QPELDSFKEE LDKYF KNHT SPDVDLGDIS GINASVVNIQ KEIDRLNEVA KNLNESLIDL QELGKYEQGS GYIPEAPRDG QAYVRKDGEW VLLSTF LGR SLEVLFQ UniProtKB: Spike glycoprotein |
-Macromolecule #3: PVI.V5-4 heavy chain
Macromolecule | Name: PVI.V5-4 heavy chain / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 25.566461 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: EVQLVESGGG VVQPGRSLRL SCAASGFTFS NYAMHWVRQA PGKGLEWVAV ISYDGSNKYY ADSVKGRFTI SRDNSKNTLY LQMNSLRAE DTAVYYCARE NNYYDSSGYS YYFDYWGQGT LVTVSGASTK GPSVFPLAPS SKSTSGGTAA LGCLVKDYFP E PVTVSWNS ...String: EVQLVESGGG VVQPGRSLRL SCAASGFTFS NYAMHWVRQA PGKGLEWVAV ISYDGSNKYY ADSVKGRFTI SRDNSKNTLY LQMNSLRAE DTAVYYCARE NNYYDSSGYS YYFDYWGQGT LVTVSGASTK GPSVFPLAPS SKSTSGGTAA LGCLVKDYFP E PVTVSWNS GALTSGVHTF PAVLQSSGLY SLSSVVTVPS SSLGTQTYIC NVNHKPSNTK VDKRVEPKSC DKLEVLFQ |
-Macromolecule #4: PVI.V5-4 light chain
Macromolecule | Name: PVI.V5-4 light chain / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 23.481055 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: EIVLTQSPGT LSLSPGERAT LSCRASQSVS SSYLAWYQQK PGQAPRLLIY GASSRATGIP DRFSGSGSGT DFTLTISRLE PEDFAVYYC QQYGSSPMCS FGQGTKVEIK RTVAAPSVFI FPPSDEQLKS GTASVVCLLN NFYPREAKVQ WKVDNALQSG N SQESVTEQ ...String: EIVLTQSPGT LSLSPGERAT LSCRASQSVS SSYLAWYQQK PGQAPRLLIY GASSRATGIP DRFSGSGSGT DFTLTISRLE PEDFAVYYC QQYGSSPMCS FGQGTKVEIK RTVAAPSVFI FPPSDEQLKS GTASVVCLLN NFYPREAKVQ WKVDNALQSG N SQESVTEQ DSKDSTYSLS STLTLSKADY EKHKVYACEV THQGLSSPVT KSFNRGEC |
-Macromolecule #6: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 6 / Number of copies: 2 / 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: 7.5 |
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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 (6k x 4k) / Average electron dose: 52.51 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: OTHER / Imaging mode: OTHER / Nominal defocus max: 2.5 µm / Nominal defocus min: 0.8 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: NONE |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.6 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 120000 |
Initial angle assignment | Type: ANGULAR RECONSTITUTION |
Final angle assignment | Type: ANGULAR RECONSTITUTION |