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Yorodumi- EMDB-26983: 1F8 mAb in complex with the computationally optimized broadly rea... -
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-Basic information
Entry | Database: EMDB / ID: EMD-26983 | |||||||||
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Title | 1F8 mAb in complex with the computationally optimized broadly reactive H1 influenza hemagglutinin P1 | |||||||||
Map data | CryoEM map of COBRA P1 HA in complex with 1F8 mAb | |||||||||
Sample |
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Keywords | Hemagglutinin / influenza virus / COBRA / monoclonal antibody / IMMUNE SYSTEM / Viral Protein-IMMUNE SYSTEM complex | |||||||||
Biological species | Homo sapiens (human) / Influenza A virus / Mus musculus (house mouse) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.1 Å | |||||||||
Authors | Dzimianski JV / DuBois RM / Ward A | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Commun Biol / Year: 2023 Title: Structural insights into the broad protection against H1 influenza viruses by a computationally optimized hemagglutinin vaccine. Authors: John V Dzimianski / Julianna Han / Giuseppe A Sautto / Sara M O'Rourke / Joseph M Cruz / Spencer R Pierce / Jeffrey W Ecker / Michael A Carlock / Kaito A Nagashima / Jarrod J Mousa / Ted M ...Authors: John V Dzimianski / Julianna Han / Giuseppe A Sautto / Sara M O'Rourke / Joseph M Cruz / Spencer R Pierce / Jeffrey W Ecker / Michael A Carlock / Kaito A Nagashima / Jarrod J Mousa / Ted M Ross / Andrew B Ward / Rebecca M DuBois / Abstract: Influenza virus poses an ongoing human health threat with pandemic potential. Due to mutations in circulating strains, formulating effective vaccines remains a challenge. The use of computationally ...Influenza virus poses an ongoing human health threat with pandemic potential. Due to mutations in circulating strains, formulating effective vaccines remains a challenge. The use of computationally optimized broadly reactive antigen (COBRA) hemagglutinin (HA) proteins is a promising vaccine strategy to protect against a wide range of current and future influenza viruses. Though effective in preclinical studies, the mechanistic basis driving the broad reactivity of COBRA proteins remains to be elucidated. Here, we report the crystal structure of the COBRA HA termed P1 and identify antigenic and glycosylation properties that contribute to its immunogenicity. We further report the cryo-EM structure of the P1-elicited broadly neutralizing antibody 1F8 bound to COBRA P1, revealing 1F8 to recognize an atypical receptor binding site epitope via an unexpected mode of binding. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_26983.map.gz | 118.2 MB | EMDB map data format | |
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Header (meta data) | emd-26983-v30.xml emd-26983.xml | 19.2 KB 19.2 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_26983_fsc.xml | 11.1 KB | Display | FSC data file |
Images | emd_26983.png | 74.9 KB | ||
Masks | emd_26983_msk_1.map | 125 MB | Mask map | |
Filedesc metadata | emd-26983.cif.gz | 6.7 KB | ||
Others | emd_26983_half_map_1.map.gz emd_26983_half_map_2.map.gz | 116 MB 116 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-26983 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-26983 | HTTPS FTP |
-Related structure data
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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-Map
File | Download / File: emd_26983.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Annotation | CryoEM map of COBRA P1 HA in complex with 1F8 mAb | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.045 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_26983_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: CryoEM half map B of COBRA P1 HA in complex with 1F8 mAb
File | emd_26983_half_map_1.map | ||||||||||||
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Annotation | CryoEM half map B of COBRA P1 HA in complex with 1F8 mAb | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: CryoEM half map A of COBRA P1 HA in complex with 1F8 mAb
File | emd_26983_half_map_2.map | ||||||||||||
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Annotation | CryoEM half map A of COBRA P1 HA in complex with 1F8 mAb | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : COBRA P1 HA in complex with 1F8 mAb
Entire | Name: COBRA P1 HA in complex with 1F8 mAb |
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Components |
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-Supramolecule #1: COBRA P1 HA in complex with 1F8 mAb
Supramolecule | Name: COBRA P1 HA in complex with 1F8 mAb / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 |
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Source (natural) | Organism: Homo sapiens (human) |
-Supramolecule #2: COBRA P1 hemagglutinin
Supramolecule | Name: COBRA P1 hemagglutinin / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1 Details: HA antigen designed from human H1N1 viruses from 1933-1957 and 2009-2011, and swine H1N1 viruses from 1931-1998. |
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Source (natural) | Organism: Influenza A virus |
-Supramolecule #3: 1F8 monoclonal antibody
Supramolecule | Name: 1F8 monoclonal antibody / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2-#3 Details: Recombinantly expressed Fab fragment of an IgG antibody. |
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Source (natural) | Organism: Mus musculus (house mouse) |
-Macromolecule #1: COBRA P1 HA
Macromolecule | Name: COBRA P1 HA / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Influenza A virus |
Molecular weight | Theoretical: 63.264535 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: DTICIGYHAN NSTDTVDTVL EKNVTVTHSV NLLEDSHNGK LCKLKGIAPL QLGKCNIAGW LLGNPECESL LSARSWSYIV ETPNSENGT CYPGDFIDYE ELREQLSSVS SFERFEIFPK ESSWPNHNTT KGVTAACSHA GKSSFYRNLL WLTKKGGSYP K LSKSYVNN ...String: DTICIGYHAN NSTDTVDTVL EKNVTVTHSV NLLEDSHNGK LCKLKGIAPL QLGKCNIAGW LLGNPECESL LSARSWSYIV ETPNSENGT CYPGDFIDYE ELREQLSSVS SFERFEIFPK ESSWPNHNTT KGVTAACSHA GKSSFYRNLL WLTKKGGSYP K LSKSYVNN KGKEVLVLWG VHHPSTSTDQ QSLYQNENAY VSVVSSNYNR RFTPEIAERP KVRGQAGRMN YYWTLLEPGD TI IFEATGN LIAPWYAFAL SRGSGSGIIT SNASMHECNT KCQTPQGAIN SSLPFQNIHP VTIGECPKYV RSTKLRMVTG LRN IPSIQS RGLFGAIAGF IEGGWTGMID GWYGYHHQNE QGSGYAADQK STQNAINGIT NKVNSVIEKM NTQFTAVGKE FNNL EKRME NLNKKVDDGF LDIWTYNAEL LVLLENERTL DFHDSNVKNL YEKVKSQLRN NAKEIGNGCF EFYHKCDNEC MESVK NGTY DYPKYSEESK LNREKIDGVK LESMGVYGSG YIPEAPRDGQ AYVRKDGEWV LLSTFLGLND IFEAQKIEWH EGHHHH HH |
-Macromolecule #2: 1F8 light chain
Macromolecule | Name: 1F8 light chain / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 23.918271 KDa |
Recombinant expression | Organism: Cricetulus griseus (Chinese hamster) |
Sequence | String: DIVLTQSPAS LAVSLGQRAT ISCKASQSVD FDGDTYMSWY QQKPGQPPKL LIYAASKLES GIPARFSGSG SGTDFTLNIH PVEEEDAAT YFCQQSNEDP WTFGGGTKLE IKRADAAPTV SIFPPSSEQL TSGGASVVCF LNNFYPKDIN VKWKIDGSER Q NGVLNSWT ...String: DIVLTQSPAS LAVSLGQRAT ISCKASQSVD FDGDTYMSWY QQKPGQPPKL LIYAASKLES GIPARFSGSG SGTDFTLNIH PVEEEDAAT YFCQQSNEDP WTFGGGTKLE IKRADAAPTV SIFPPSSEQL TSGGASVVCF LNNFYPKDIN VKWKIDGSER Q NGVLNSWT DQDSKDSTYS MSSTLTLTKD EYERHNSYTC EATHKTSTSP IVKSFNRNEC |
-Macromolecule #3: 1F8 heavy chain
Macromolecule | Name: 1F8 heavy chain / type: protein_or_peptide / ID: 3 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 23.900818 KDa |
Recombinant expression | Organism: Cricetulus griseus (Chinese hamster) |
Sequence | String: QVQLQQSGAE LMKPGASVKI SCKATGYTFS SYWIEWVKQR PGHGLEWIGE ILPGSGRTNY DERFKGKATF TADTSSNTAY MQLSSLTSE DSAVYYCARP RIYGMDYWGQ GTSVTVSSAK TTPPSVYPLA PGSAAQTNSM VTLGCLVKGY FPEPVTVTWN S GSLSSGVH ...String: QVQLQQSGAE LMKPGASVKI SCKATGYTFS SYWIEWVKQR PGHGLEWIGE ILPGSGRTNY DERFKGKATF TADTSSNTAY MQLSSLTSE DSAVYYCARP RIYGMDYWGQ GTSVTVSSAK TTPPSVYPLA PGSAAQTNSM VTLGCLVKGY FPEPVTVTWN S GSLSSGVH TFPAVLQSDL YTLSSSVTVP SSPRPSETVT CNVAHPASST KVDKKIEPRG LVPR |
-Macromolecule #7: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 7 / Number of copies: 10 / 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
Concentration | 0.8 mg/mL |
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Buffer | pH: 7.4 / Details: TBS |
Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 400 / Pretreatment - Type: PLASMA CLEANING |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Instrument: FEI VITROBOT MARK IV |
Details | 1:3:3 molar ratio of P1 HA, 1F8, and P1-05 |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | C2 aperture diameter: 70.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Cs: 2.7 mm / Nominal defocus max: 1.8 µm / Nominal defocus min: 0.8 µm |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Average electron dose: 50.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |