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Yorodumi- EMDB-16473: SARS-CoV-2 spike in complex with the 17T2 neutralizing antibody F... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-16473 | |||||||||
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Title | SARS-CoV-2 spike in complex with the 17T2 neutralizing antibody Fab fragment (local refinement of RBD and Fab) | |||||||||
Map data | Post processing (DeepEMhancer) of the local refinement done in cryosparc (cut). | |||||||||
Sample |
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Keywords | Complex SARS-CoV-2 Spike S 17T2 / VIRAL PROTEIN | |||||||||
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 / 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 | Severe acute respiratory syndrome coronavirus / Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.41 Å | |||||||||
Authors | Modrego A / Carlero D / Bueno-Carrasco MT / Santiago C / Carolis C / Arranz R / Blanco J / Magri G | |||||||||
Funding support | Spain, 2 items
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Citation | Journal: Nat Commun / Year: 2024 Title: A monoclonal antibody targeting a large surface of the receptor binding motif shows pan-neutralizing SARS-CoV-2 activity. Authors: Leire de Campos-Mata / Benjamin Trinité / Andrea Modrego / Sonia Tejedor Vaquero / Edwards Pradenas / Anna Pons-Grífols / Natalia Rodrigo Melero / Diego Carlero / Silvia Marfil / César ...Authors: Leire de Campos-Mata / Benjamin Trinité / Andrea Modrego / Sonia Tejedor Vaquero / Edwards Pradenas / Anna Pons-Grífols / Natalia Rodrigo Melero / Diego Carlero / Silvia Marfil / César Santiago / Dàlia Raïch-Regué / María Teresa Bueno-Carrasco / Ferran Tarrés-Freixas / Ferran Abancó / Victor Urrea / Nuria Izquierdo-Useros / Eva Riveira-Muñoz / Ester Ballana / Mónica Pérez / Júlia Vergara-Alert / Joaquim Segalés / Carlo Carolis / Rocío Arranz / Julià Blanco / Giuliana Magri / Abstract: Here we report the characterization of 17T2, a SARS-CoV-2 pan-neutralizing human monoclonal antibody isolated from a COVID-19 convalescent individual infected during the first pandemic wave. 17T2 is ...Here we report the characterization of 17T2, a SARS-CoV-2 pan-neutralizing human monoclonal antibody isolated from a COVID-19 convalescent individual infected during the first pandemic wave. 17T2 is a class 1 VH1-58/κ3-20 antibody, derived from a receptor binding domain (RBD)-specific IgA memory B cell, with a broad neutralizing activity against former and new SARS-CoV-2 variants, including XBB.1.16 and BA.2.86 Omicron subvariants. Consistently, 17T2 demonstrates in vivo prophylactic and therapeutic activity against Omicron BA.1.1 infection in K18-hACE2 mice. Cryo-electron microscopy reconstruction shows that 17T2 binds the BA.1 spike with the RBD in "up" position and blocks the receptor binding motif, as other structurally similar antibodies do, including S2E12. Yet, unlike S2E12, 17T2 retains its neutralizing activity against all variants tested, probably due to a larger RBD contact area. These results highlight the impact of small structural antibody changes on neutralizing performance and identify 17T2 as a potential candidate for future clinical interventions. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_16473.map.gz | 228.7 MB | EMDB map data format | |
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Header (meta data) | emd-16473-v30.xml emd-16473.xml | 18.8 KB 18.8 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_16473_fsc.xml | 13.3 KB | Display | FSC data file |
Images | emd_16473.png | 27.2 KB | ||
Filedesc metadata | emd-16473.cif.gz | 6.4 KB | ||
Others | emd_16473_half_map_1.map.gz emd_16473_half_map_2.map.gz | 422 MB 422 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-16473 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-16473 | HTTPS FTP |
-Validation report
Summary document | emd_16473_validation.pdf.gz | 576.7 KB | Display | EMDB validaton report |
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Full document | emd_16473_full_validation.pdf.gz | 576.3 KB | Display | |
Data in XML | emd_16473_validation.xml.gz | 25.1 KB | Display | |
Data in CIF | emd_16473_validation.cif.gz | 33.3 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-16473 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-16473 | HTTPS FTP |
-Related structure data
Related structure data | 8c89MC 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_16473.map.gz / Format: CCP4 / Size: 454.3 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Annotation | Post processing (DeepEMhancer) of the local refinement done in cryosparc (cut). | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.855 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: Half map A of the local refinement done in cryosparc.
File | emd_16473_half_map_1.map | ||||||||||||
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Annotation | Half map A of the local refinement done in cryosparc. | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map B of the local refinement done in cryosparc.
File | emd_16473_half_map_2.map | ||||||||||||
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Annotation | Half map B of the local refinement done in cryosparc. | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : SARS-CoV-2 Omicron Variant Spike Trimer in complex with three 17T...
Entire | Name: SARS-CoV-2 Omicron Variant Spike Trimer in complex with three 17T2 Fabs |
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Components |
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-Supramolecule #1: SARS-CoV-2 Omicron Variant Spike Trimer in complex with three 17T...
Supramolecule | Name: SARS-CoV-2 Omicron Variant Spike Trimer in complex with three 17T2 Fabs type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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-Supramolecule #2: Spike glycoprotein RBD
Supramolecule | Name: Spike glycoprotein RBD / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus |
-Supramolecule #3: 17T2 Fab
Supramolecule | Name: 17T2 Fab / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2-#3 |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Spike protein S2'
Macromolecule | Name: Spike protein S2' / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus |
Molecular weight | Theoretical: 23.898064 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: ESIVRFPNIT NLCPFDEVFN ATRFASVYAW NRKRISNCVA DYSVLYNLAP FFTFKCYGVS PTKLNDLCFT NVYADSFVIR GDEVRQIAP GQTGNIADYN YKLPDDFTGC VIAWNSNKLD SKVSGNYNYL YRLFRKSNLK PFERDISTEI YQAGNKPCNG V AGFNCYFP ...String: ESIVRFPNIT NLCPFDEVFN ATRFASVYAW NRKRISNCVA DYSVLYNLAP FFTFKCYGVS PTKLNDLCFT NVYADSFVIR GDEVRQIAP GQTGNIADYN YKLPDDFTGC VIAWNSNKLD SKVSGNYNYL YRLFRKSNLK PFERDISTEI YQAGNKPCNG V AGFNCYFP LRSYSFRPTY GVGHQPYRVV VLSFELLHAP ATVCGPKKST NL UniProtKB: Spike glycoprotein |
-Macromolecule #2: 17T2 Fab heavy chain
Macromolecule | Name: 17T2 Fab heavy 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: 24.231311 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: QVQLVQSGPE VKKPGTSVKV SCKAPVFTFS ISAVQWVRQA RGQRLEWIGW IVVGSGNTNY AQNFQERVTI TTDMSTGTVY MELSGLRSE DTAMYYCAAP YCNRTTCYDG FDLWGQGTMV TVSSASTKGP SVFPLAPSSK STSGGTAALG CLVKDYFPEP V TVSWNSGA ...String: QVQLVQSGPE VKKPGTSVKV SCKAPVFTFS ISAVQWVRQA RGQRLEWIGW IVVGSGNTNY AQNFQERVTI TTDMSTGTVY MELSGLRSE DTAMYYCAAP YCNRTTCYDG FDLWGQGTMV TVSSASTKGP SVFPLAPSSK STSGGTAALG CLVKDYFPEP V TVSWNSGA LTSGVHTFPA VLQSSGLYSL SSVVTVPSSS LGTQTYICNV NHKPSNTKVD KRVEPKSC |
-Macromolecule #3: 17T2 Fab light chain
Macromolecule | Name: 17T2 Fab light 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: 23.686299 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: EIVLTQSPGT LSLSPGERAT LSCRASQSIS SNYLAWYQQK PGQAPRLLIY GASSRATGIP DRFSGSGSGT DFTLSINRLE PEDFAMYYC QHYGGLSRWT FGQGTKVEIK RTVAAPSVFI FPPSDEQLKS GTASVVCLLN NFYPREAKVQ WKVDNALQSG N SQESVTEQ ...String: EIVLTQSPGT LSLSPGERAT LSCRASQSIS SNYLAWYQQK PGQAPRLLIY GASSRATGIP DRFSGSGSGT DFTLSINRLE PEDFAMYYC QHYGGLSRWT FGQGTKVEIK 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: 7.6 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | TFS TALOS F200C |
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Image recording | Film or detector model: FEI FALCON III (4k x 4k) / Average electron dose: 32.0 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: OTHER / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.0 µm |
Experimental equipment | Model: Tecnai F20 / Image courtesy: FEI Company |