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Yorodumi- EMDB-47928: Cryo-EM structure of SARS-CoV-2 spike protein in complex with hum... -
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Basic information
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| Title | Cryo-EM structure of SARS-CoV-2 spike protein in complex with human neutralizing antibody WRAIR-2008 (focused refinement of NTD and WRAIR-2008) | |||||||||
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Keywords | viral protein / immune system / antibody / human antibody / neutralizing antibody / SARS-CoV-2 / HexaPro / VIRAL PROTEIN-IMMUNE SYSTEM complex | |||||||||
| Function / homology | Function and homology informationsymbiont-mediated disruption of host tissue / Maturation of spike protein / Translation of Structural Proteins / Virion Assembly and Release / host cell surface / host extracellular space / viral translation / symbiont-mediated-mediated suppression of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion ...symbiont-mediated disruption of host tissue / Maturation of spike protein / Translation of Structural Proteins / Virion Assembly and Release / host cell surface / host extracellular space / viral translation / symbiont-mediated-mediated suppression of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion / membrane fusion / entry receptor-mediated virion attachment to host cell / Attachment and Entry / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / positive regulation of viral entry into host cell / receptor-mediated virion attachment to host cell / host cell surface receptor binding / symbiont-mediated suppression of host innate immune response / receptor ligand activity / endocytosis involved in viral entry into host cell / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / symbiont entry into host cell / 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) | |||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 3.89 Å | |||||||||
Authors | Jensen JL / Thomas PV / Joyce MG | |||||||||
| Funding support | United States, 1 items
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Citation | Journal: mBio / Year: 2025Title: First-generation N-terminal domain supersite public antibodies retain activity against Omicron-derived lineages and protect mice against Omicron BA.5 challenge. Authors: Vincent Dussupt / Jaime L Jensen / Paul V Thomas / Letzibeth Mendez-Rivera / Kerri G Lal / Michelle Zemil McCrea / Isabella Swafford / Joana Hernandez / Rajeshwer S Sankhala / Mekhala Rao / ...Authors: Vincent Dussupt / Jaime L Jensen / Paul V Thomas / Letzibeth Mendez-Rivera / Kerri G Lal / Michelle Zemil McCrea / Isabella Swafford / Joana Hernandez / Rajeshwer S Sankhala / Mekhala Rao / Juhi Arora / Agnes Hajduczki / Ningbo Jian / Phyllis A Rees / Indica Showell-De Leon / Gabriel Smith / Lauren Smith / Diana Wasson / Annika Schmid / I-Ting Teng / Tongqing Zhou / Peter D Kwong / Jeffrey R Currier / William W Reiley / Dominic Paquin-Proulx / Victoria R Polonis / Natalie D Collins / Nelson L Michael / M Gordon Joyce / Shelly J Krebs / ![]() Abstract: Monoclonal antibodies to SARS-CoV-2 can offer prophylactic and therapeutic protection against severe disease, with particular utility for immunosuppressed and vulnerable populations. With the ...Monoclonal antibodies to SARS-CoV-2 can offer prophylactic and therapeutic protection against severe disease, with particular utility for immunosuppressed and vulnerable populations. With the constant emergence of new variants, understanding the neutralizing potency of monoclonal antibodies to dynamic spike protein epitopes is crucial. We show that a set of VH1-24-derived N-terminal domain (NTD)-directed antibodies, isolated from a convalescent donor early in the pandemic, displayed remarkable neutralization resilience against many Omicron SARS-CoV-2 variants, including BA.2, BA.5, and BQ.1.1. Neutralization potency to these Omicron variants is associated with slower off-rates to the spike protein. Structural characterization of the most potent NTD antibody, WRAIR-2008, revealed a conserved mode of interaction shared with other antibodies of the same multi-donor class. WRAIR-2008 protected mice from weight loss following BA.5 challenge and reduced infectious viral titers in the lungs. Our study highlights the retention of neutralization activity and protection of first-generation VH1-24-derived NTD-directed antibodies to specific Omicron variants and provides valuable insights into the shifting landscape of SARS-CoV-2 variants that are vulnerable to select monoclonal antibodies. IMPORTANCE: As SARS-CoV-2 circulating variants evolve, it is important to understand the vulnerabilities of these viruses to neutralizing antibodies. Within this manuscript, we describe first- ...IMPORTANCE: As SARS-CoV-2 circulating variants evolve, it is important to understand the vulnerabilities of these viruses to neutralizing antibodies. Within this manuscript, we describe first-generation antibodies isolated following infection with WA-1 that retain viral neutralization to subsequent Omicron variants by targeting a site of viral vulnerability called the NTD. This work highlights the shifting landscape of SARS-CoV-2 variants and provides mechanistic insights into how antibodies from prior infections may play a role in preventing subsequent SARS-CoV-2 variant infections. | |||||||||
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Structure visualization
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Downloads & links
-EMDB archive
| Map data | emd_47928.map.gz | 262.1 MB | EMDB map data format | |
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| Header (meta data) | emd-47928-v30.xml emd-47928.xml | 23.6 KB 23.6 KB | Display Display | EMDB header |
| FSC (resolution estimation) | emd_47928_fsc.xml | 17 KB | Display | FSC data file |
| Images | emd_47928.png | 63 KB | ||
| Filedesc metadata | emd-47928.cif.gz | 8.1 KB | ||
| Others | emd_47928_half_map_1.map.gz emd_47928_half_map_2.map.gz | 474.3 MB 474.3 MB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-47928 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-47928 | HTTPS FTP |
-Validation report
| Summary document | emd_47928_validation.pdf.gz | 853.7 KB | Display | EMDB validaton report |
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| Full document | emd_47928_full_validation.pdf.gz | 853.2 KB | Display | |
| Data in XML | emd_47928_validation.xml.gz | 26.2 KB | Display | |
| Data in CIF | emd_47928_validation.cif.gz | 34.8 KB | Display | |
| Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-47928 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-47928 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 9eczMC ![]() 9ecxC ![]() 9ecyC ![]() 9mi3C M: atomic model generated by this map C: citing same article ( |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
| EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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| Related items in Molecule of the Month |
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Map
| File | Download / File: emd_47928.map.gz / Format: CCP4 / Size: 512 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: 1.02 Å | ||||||||||||||||||||||||||||||||||||
| Density |
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| Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
| Details | EMDB XML:
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-Supplemental data
-Half map: Half map B
| File | emd_47928_half_map_1.map | ||||||||||||
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| Annotation | Half map B | ||||||||||||
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| Density Histograms |
-Half map: Half map A
| File | emd_47928_half_map_2.map | ||||||||||||
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| Annotation | Half map A | ||||||||||||
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| Density Histograms |
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Sample components
-Entire : WRAIR-2008 antibody Fab bound to the N-terminal domain of the spi...
| Entire | Name: WRAIR-2008 antibody Fab bound to the N-terminal domain of the spike glycoprotein (focused refinement) |
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| Components |
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-Supramolecule #1: WRAIR-2008 antibody Fab bound to the N-terminal domain of the spi...
| Supramolecule | Name: WRAIR-2008 antibody Fab bound to the N-terminal domain of the spike glycoprotein (focused refinement) type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 |
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| Source (natural) | Organism: ![]() |
-Macromolecule #1: Spike glycoprotein
| Macromolecule | Name: Spike glycoprotein / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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| Source (natural) | Organism: ![]() |
| Molecular weight | Theoretical: 142.427438 KDa |
| Recombinant expression | Organism: Homo sapiens (human) |
| Sequence | String: MFVFLVLLPL VSSQCVNLTT RTQLPPAYTN SFTRGVYYPD KVFRSSVLHS TQDLFLPFFS NVTWFHAIHV SGTNGTKRFD NPVLPFNDG VYFASTEKSN IIRGWIFGTT LDSKTQSLLI VNNATNVVIK VCEFQFCNDP FLGVYYHKNN KSWMESEFRV Y SSANNCTF ...String: MFVFLVLLPL VSSQCVNLTT RTQLPPAYTN SFTRGVYYPD KVFRSSVLHS TQDLFLPFFS NVTWFHAIHV SGTNGTKRFD NPVLPFNDG VYFASTEKSN IIRGWIFGTT LDSKTQSLLI VNNATNVVIK VCEFQFCNDP FLGVYYHKNN KSWMESEFRV Y SSANNCTF EYVSQPFLMD LEGKQGNFKN LREFVFKNID GYFKIYSKHT PINLVRDLPQ GFSALEPLVD LPIGINITRF QT LLALHRS YLTPGDSSSG WTAGAAAYYV GYLQPRTFLL KYNENGTITD AVDCALDPLS ETKCTLKSFT VEKGIYQTSN FRV QPTESI VRFPNITNLC PFGEVFNATR FASVYAWNRK RISNCVADYS VLYNSASFST FKCYGVSPTK LNDLCFTNVY ADSF VIRGD EVRQIAPGQT GKIADYNYKL PDDFTGCVIA WNSNNLDSKV GGNYNYLYRL FRKSNLKPFE RDISTEIYQA GSTPC NGVE GFNCYFPLQS YGFQPTNGVG YQPYRVVVLS FELLHAPATV CGPKKSTNLV KNKCVNFNFN GLTGTGVLTE SNKKFL PFQ QFGRDIADTT DAVRDPQTLE ILDITPCSFG GVSVITPGTN TSNQVAVLYQ DVNCTEVPVA IHADQLTPTW RVYSTGS NV FQTRAGCLIG AEHVNNSYEC DIPIGAGICA SYQTQTNSPG SASSVASQSI IAYTMSLGAE NSVAYSNNSI AIPTNFTI S VTTEILPVSM TKTSVDCTMY ICGDSTECSN LLLQYGSFCT QLNRALTGIA VEQDKNTQEV FAQVKQIYKT PPIKDFGGF NFSQILPDPS KPSKRSPIED LLFNKVTLAD AGFIKQYGDC LGDIAARDLI CAQKFNGLTV LPPLLTDEMI AQYTSALLAG TITSGWTFG AGPALQIPFP MQMAYRFNGI GVTQNVLYEN QKLIANQFNS AIGKIQDSLS STPSALGKLQ DVVNQNAQAL N TLVKQLSS NFGAISSVLN DILSRLDPPE AEVQIDRLIT GRLQSLQTYV TQQLIRAAEI RASANLAATK MSECVLGQSK RV DFCGKGY HLMSFPQSAP HGVVFLHVTY VPAQEKNFTT APAICHDGKA HFPREGVFVS NGTHWFVTQR NFYEPQIITT DNT FVSGNC DVVIGIVNNT VYDPLQPELD SFKEELDKYF KNHTSPDVDL GDISGINASV VNIQKEIDRL NEVAKNLNES LIDL QELGK YEQGSGYIPE APRDGQAYVR KDGEWVLLST FLGRSLEVLF QGPGHHHHHH HHSAWSHPQF EKGGGSGGGG SGGSA WSHP QFEK UniProtKB: Spike glycoprotein |
-Macromolecule #2: WRAIR-2008 antibody Fab heavy chain
| Macromolecule | Name: WRAIR-2008 antibody 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: 24.786604 KDa |
| Recombinant expression | Organism: Homo sapiens (human) |
| Sequence | String: QVRVVQSGAE VKNPGASVKV SCKVSGYTLT ELSIHWVRQA PGNGLEWMGG FDPEDGETIY AQKFQGRVTM TEDTSTDTAY MELSSLRSD DTAVYYCATA GAITGTPRNF YYYYGMDVWG QGTTVTVSSA STKGPSVFPL APSSKSTSGG TAALGCLVKD Y FPEPVTVS ...String: QVRVVQSGAE VKNPGASVKV SCKVSGYTLT ELSIHWVRQA PGNGLEWMGG FDPEDGETIY AQKFQGRVTM TEDTSTDTAY MELSSLRSD DTAVYYCATA GAITGTPRNF YYYYGMDVWG QGTTVTVSSA STKGPSVFPL APSSKSTSGG TAALGCLVKD Y FPEPVTVS WNSGALTSGV HTFPAVLQSS GLYSLSSVVT VPSSSLGTQT YICNVNHKPS NTKVDKKVEP KSCDK |
-Macromolecule #3: WRAIR-2008 antibody Fab light chain
| Macromolecule | Name: WRAIR-2008 antibody 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: 24.106947 KDa |
| Recombinant expression | Organism: Homo sapiens (human) |
| Sequence | String: DIVMTQTPLS SPVTLGQPAS ISCRSSQSLV HSDGNTYLSW LQQRPGQPPR LLIYKISNRF SGVPDRFSGS GAGTDFTLKI SRVEAEDVG VYYCMQVTQF PYTFGQGTKL EIKRTVAAPS VFIFPPSDEQ LKSGTASVVC LLNNFYPREA KVQWKVDNAL Q SGNSQESV ...String: DIVMTQTPLS SPVTLGQPAS ISCRSSQSLV HSDGNTYLSW LQQRPGQPPR LLIYKISNRF SGVPDRFSGS GAGTDFTLKI SRVEAEDVG VYYCMQVTQF PYTFGQGTKL EIKRTVAAPS VFIFPPSDEQ LKSGTASVVC LLNNFYPREA KVQWKVDNAL Q SGNSQESV TEQDSKDSTY SLSSTLTLSK ADYEKHKVYA CEVTHQGLSS PVTKSFNRGE C |
-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 |
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Sample preparation
| Buffer | pH: 7.4 / Details: PBS + 2% v/v glycerol |
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| Grid | Model: Quantifoil R0.6/1 / Material: COPPER / Mesh: 400 / Support film - Material: CARBON / Support film - topology: CONTINUOUS / Pretreatment - Type: GLOW DISCHARGE |
| Vitrification | Cryogen name: ETHANE / Instrument: LEICA EM GP |
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Electron microscopy
| Microscope | JEOL CRYO ARM 200 |
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| Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 50.0 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: 3.2 µm / Nominal defocus min: 0.1 µm |
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Keywords
Homo sapiens (human)
Authors
United States, 1 items
Citation








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Processing
FIELD EMISSION GUN

