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Yorodumi- EMDB-27438: Cryo-EM structure of SARS-CoV-2 Beta (B.1.351) spike protein in c... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-27438 | |||||||||
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Title | Cryo-EM structure of SARS-CoV-2 Beta (B.1.351) spike protein in complex with VH domain F6 | |||||||||
Map data | ||||||||||
Sample |
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Biological species | Severe acute respiratory syndrome coronavirus 2 / Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.83 Å | |||||||||
Authors | Zhu X / Saville JW / Mannar D / Berezuk AM / Subramaniam S | |||||||||
Funding support | Canada, 2 items
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Citation | Journal: iScience / Year: 2022 Title: Potent and broad neutralization of SARS-CoV-2 variants of concern (VOCs) including omicron sub-lineages BA.1 and BA.2 by biparatopic human VH domains. Authors: Chuan Chen / James W Saville / Michelle M Marti / Alexandra Schäfer / Mary Hongying Cheng / Dhiraj Mannar / Xing Zhu / Alison M Berezuk / Anupam Banerjee / Michele D Sobolewski / Andrew Kim ...Authors: Chuan Chen / James W Saville / Michelle M Marti / Alexandra Schäfer / Mary Hongying Cheng / Dhiraj Mannar / Xing Zhu / Alison M Berezuk / Anupam Banerjee / Michele D Sobolewski / Andrew Kim / Benjamin R Treat / Priscila Mayrelle Da Silva Castanha / Nathan Enick / Kevin D McCormick / Xianglei Liu / Cynthia Adams / Margaret Grace Hines / Zehua Sun / Weizao Chen / Jana L Jacobs / Simon M Barratt-Boyes / John W Mellors / Ralph S Baric / Ivet Bahar / Dimiter S Dimitrov / Sriram Subramaniam / David R Martinez / Wei Li / Abstract: The emergence of SARS-CoV-2 variants of concern (VOCs) requires the development of next-generation biologics with high neutralization breadth. Here, we characterized a human V domain, F6, which we ...The emergence of SARS-CoV-2 variants of concern (VOCs) requires the development of next-generation biologics with high neutralization breadth. Here, we characterized a human V domain, F6, which we generated by sequentially panning large phage-displayed V libraries against receptor binding domains (RBDs) containing VOC mutations. Cryo-EM analyses reveal that F6 has a unique binding mode that spans a broad surface of the RBD and involves the antibody framework region. Attachment of an Fc region to a fusion of F6 and ab8, a previously characterized V domain, resulted in a construct (F6-ab8-Fc) that broadly and potently neutralized VOCs including Omicron. Additionally, prophylactic treatment using F6-ab8-Fc reduced live Beta (B.1.351) variant viral titers in the lungs of a mouse model. Our results provide a new potential therapeutic against SARS-CoV-2 variants including Omicron and highlight a vulnerable epitope within the spike that may be exploited to achieve broad protection against circulating variants. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_27438.map.gz | 123.3 MB | EMDB map data format | |
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Header (meta data) | emd-27438-v30.xml emd-27438.xml | 17.4 KB 17.4 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_27438_fsc.xml | 13.8 KB | Display | FSC data file |
Images | emd_27438.png | 113.1 KB | ||
Others | emd_27438_half_map_1.map.gz emd_27438_half_map_2.map.gz | 226.6 MB 226.6 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-27438 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-27438 | HTTPS FTP |
-Validation report
Summary document | emd_27438_validation.pdf.gz | 1022.9 KB | Display | EMDB validaton report |
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Full document | emd_27438_full_validation.pdf.gz | 1022.5 KB | Display | |
Data in XML | emd_27438_validation.xml.gz | 19.4 KB | Display | |
Data in CIF | emd_27438_validation.cif.gz | 25.5 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-27438 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-27438 | HTTPS FTP |
-Related structure data
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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-Map
File | Download / File: emd_27438.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 1 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #1
File | emd_27438_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_27438_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : SARS-CoV-2 Beta (B.1.351) spike protein in complex with VH domain F6
Entire | Name: SARS-CoV-2 Beta (B.1.351) spike protein in complex with VH domain F6 |
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Components |
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-Supramolecule #1: SARS-CoV-2 Beta (B.1.351) spike protein in complex with VH domain F6
Supramolecule | Name: SARS-CoV-2 Beta (B.1.351) spike protein in complex with VH domain F6 type: complex / Chimera: Yes / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
-Supramolecule #2: SARS-CoV-2 Beta (B.1.351) spike protein
Supramolecule | Name: SARS-CoV-2 Beta (B.1.351) spike protein / type: complex / Chimera: Yes / ID: 2 / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
Recombinant expression | Organism: Homo sapiens (human) |
-Supramolecule #3: VH F6
Supramolecule | Name: VH F6 / type: complex / Chimera: Yes / ID: 3 / Parent: 1 / Macromolecule list: #2 |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Escherichia coli (E. coli) |
-Macromolecule #1: SARS-CoV-2 Beta (B.1.351) spike protein
Macromolecule | Name: SARS-CoV-2 Beta (B.1.351) spike protein / type: protein_or_peptide / ID: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
Sequence | String: MFVFLVLLPL VSSQCVNFTT RTQLPPAYTN SFTRGVYYPD KVFRSSVLHS TQDLFLPFFS NVTWFHAIHV SGTNGTKRFA NPVLPFNDGV YFASTEKSNI IRGWIFGTTL DSKTQSLLIV NNATNVVIKV CEFQFCNDPF LGVYYHKNNK SWMESEFRVY SSANNCTFEY ...String: MFVFLVLLPL VSSQCVNFTT RTQLPPAYTN SFTRGVYYPD KVFRSSVLHS TQDLFLPFFS NVTWFHAIHV SGTNGTKRFA NPVLPFNDGV YFASTEKSNI IRGWIFGTTL DSKTQSLLIV NNATNVVIKV CEFQFCNDPF LGVYYHKNNK SWMESEFRVY SSANNCTFEY VSQPFLMDLE GKQGNFKNLR EFVFKNIDGY FKIYSKHTPI NLVRGLPQGF SALEPLVDLP IGINITRFQT LLALHISYLT PGDSSSGWTA GAAAYYVGYL QPRTFLLKYN ENGTITDAVD CALDPLSETK CTLKSFTVEK GIYQTSNFRV QPTESIVRFP NITNLCPFGE VFNATRFASV YAWNRKRISN CVADYSVLYN SASFSTFKCY GVSPTKLNDL CFTNVYADSF VIRGDEVRQI APGQTGNIAD YNYKLPDDFT GCVIAWNSNN LDSKVGGNYN YLYRLFRKSN LKPFERDIST EIYQAGSTPC NGVKGFNCYF PLQSYGFQPT YGVGYQPYRV VVLSFELLHA PATVCGPKKS TNLVKNKCVN FNFNGLTGTG VLTESNKKFL PFQQFGRDIA DTTDAVRDPQ TLEILDITPC SFGGVSVITP GTNTSNQVAV LYQGVNCTEV PVAIHADQLT PTWRVYSTGS NVFQTRAGCL IGAEHVNNSY ECDIPIGAGI CASYQTQTNS PGSASSVASQ SIIAYTMSLG VENSVAYSNN SIAIPTNFTI SVTTEILPVS MTKTSVDCTM YICGDSTECS NLLLQYGSFC TQLNRALTGI AVEQDKNTQE VFAQVKQIYK TPPIKDFGGF NFSQILPDPS KPSKRSPIED LLFNKVTLAD AGFIKQYGDC LGDIAARDLI CAQKFNGLTV LPPLLTDEMI AQYTSALLAG TITSGWTFGA GPALQIPFPM QMAYRFNGIG VTQNVLYENQ KLIANQFNSA IGKIQDSLSS TPSALGKLQD VVNQNAQALN TLVKQLSSNF GAISSVLNDI LSRLDPPEAE VQIDRLITGR LQSLQTYVTQ QLIRAAEIRA SANLAATKMS ECVLGQSKRV DFCGKGYHLM SFPQSAPHGV VFLHVTYVPA QEKNFTTAPA ICHDGKAHFP REGVFVSNGT HWFVTQRNFY EPQIITTDNT FVSGNCDVVI GIVNNTVYDP LQPELDSFKE ELDKYFKNHT SPDVDLGDIS GINASVVNIQ KEIDRLNEVA KNLNESLIDL QELGKYEQGS GYIPEAPRDG QAYVRKDGEW VLLSTFLGRS LEVLFQGPGH HHHHHHHSAW SHPQFEKGGG SGGGGSGGSA WSHPQFEK |
-Macromolecule #2: VH F6
Macromolecule | Name: VH F6 / type: protein_or_peptide / ID: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Sequence | String: EVQLVESGGG LVQPGGSLRL SCAASDFDFY DYEMSWVRQA PGKALEWIGN IYYSGDTFYN PSLKSRVTIS RDNSKNTLYL QMNSLRAEDT ATYYCARVES GSGWLDFWGQ GTLVTVSS |
-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 | TFS KRIOS |
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Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 40.0 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: 3.0 µm / Nominal defocus min: 0.5 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |