+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-26605 | |||||||||
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Title | H1 Solomon Islands 2006 hemagglutinin in complex with Ab109 | |||||||||
Map data | H1 Solomon Islands 2006 in complex with ab109 | |||||||||
Sample |
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Function / homology | Function and homology information viral budding from plasma membrane / clathrin-dependent endocytosis of virus by host cell / host cell surface receptor binding / apical plasma membrane / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / host cell plasma membrane / virion membrane Similarity search - Function | |||||||||
Biological species | Influenza A virus (A/Solomon Islands/3/2006(H1N1)) / Mus musculus (house mouse) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.36 Å | |||||||||
Authors | Windsor IW / Caradonna TM / Schmidt AG | |||||||||
Funding support | United States, 2 items
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Citation | Journal: Cell Rep / Year: 2022 Title: An epitope-enriched immunogen expands responses to a conserved viral site. Authors: Timothy M Caradonna / Larance Ronsard / Ashraf S Yousif / Ian W Windsor / Rachel Hecht / Thalia Bracamonte-Moreno / Anne A Roffler / Max J Maron / Daniel P Maurer / Jared Feldman / Elisa ...Authors: Timothy M Caradonna / Larance Ronsard / Ashraf S Yousif / Ian W Windsor / Rachel Hecht / Thalia Bracamonte-Moreno / Anne A Roffler / Max J Maron / Daniel P Maurer / Jared Feldman / Elisa Marchiori / Ralston M Barnes / Daniel Rohrer / Nils Lonberg / Thomas H Oguin / Gregory D Sempowski / Thomas B Kepler / Masayuki Kuraoka / Daniel Lingwood / Aaron G Schmidt / Abstract: Pathogens evade host humoral responses by accumulating mutations in surface antigens. While variable, there are conserved regions that cannot mutate without compromising fitness. Antibodies targeting ...Pathogens evade host humoral responses by accumulating mutations in surface antigens. While variable, there are conserved regions that cannot mutate without compromising fitness. Antibodies targeting these conserved epitopes are often broadly protective but remain minor components of the repertoire. Rational immunogen design leverages a structural understanding of viral antigens to modulate humoral responses to favor these responses. Here, we report an epitope-enriched immunogen presenting a higher copy number of the influenza hemagglutinin (HA) receptor-binding site (RBS) epitope relative to other B cell epitopes. Immunization in a partially humanized murine model imprinted with an H1 influenza shows H1-specific serum and >99% H1-specific B cells being RBS-directed. Single B cell analyses show a genetically restricted response that structural analysis defines as RBS-directed antibodies engaging the RBS with germline-encoded contacts. These data show how epitope enrichment expands B cell responses toward conserved epitopes and advances immunogen design approaches for next-generation viral vaccines. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_26605.map.gz | 127.9 MB | EMDB map data format | |
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Header (meta data) | emd-26605-v30.xml emd-26605.xml | 15 KB 15 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_26605_fsc.xml | 11.8 KB | Display | FSC data file |
Images | emd_26605.png | 99.7 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-26605 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-26605 | HTTPS FTP |
-Validation report
Summary document | emd_26605_validation.pdf.gz | 550.6 KB | Display | EMDB validaton report |
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Full document | emd_26605_full_validation.pdf.gz | 550.2 KB | Display | |
Data in XML | emd_26605_validation.xml.gz | 12.3 KB | Display | |
Data in CIF | emd_26605_validation.cif.gz | 16.4 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-26605 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-26605 | HTTPS FTP |
-Related structure data
Related structure data | 7ummMC 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_26605.map.gz / Format: CCP4 / Size: 137.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Annotation | H1 Solomon Islands 2006 in complex with ab109 | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.825 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Sample components
-Entire : hemagglutinin H1 Solomon Islands/03/2006 in complex with ab109 Fab
Entire | Name: hemagglutinin H1 Solomon Islands/03/2006 in complex with ab109 Fab |
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Components |
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-Supramolecule #1: hemagglutinin H1 Solomon Islands/03/2006 in complex with ab109 Fab
Supramolecule | Name: hemagglutinin H1 Solomon Islands/03/2006 in complex with ab109 Fab type: complex / Chimera: Yes / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 |
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-Supramolecule #2: Hemagglutinin
Supramolecule | Name: Hemagglutinin / type: complex / Chimera: Yes / ID: 2 / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: Influenza A virus (A/Solomon Islands/3/2006(H1N1)) |
Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
-Supramolecule #3: ab109 Fab heavy chain, ab 109 Fab light chain
Supramolecule | Name: ab109 Fab heavy chain, ab 109 Fab light chain / type: complex / Chimera: Yes / ID: 3 / Parent: 1 / Macromolecule list: #2-#3 |
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Source (natural) | Organism: Mus musculus (house mouse) |
Recombinant expression | Organism: Homo sapiens (human) |
-Macromolecule #1: Hemagglutinin
Macromolecule | Name: Hemagglutinin / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Influenza A virus (A/Solomon Islands/3/2006(H1N1)) Strain: A/Solomon Islands/3/2006(H1N1) |
Molecular weight | Theoretical: 58.608316 KDa |
Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
Sequence | String: ADPGYLLEDT ICIGYHANNS TDTVDTVLEK NVTVTHSVNL LEDSHNGKLC LLKGIAPLQL GNCSVAGWIL GNPECELLIS RESWSYIVE KPNPENGTCY PGHFADYEEL REQLSSVSSF ERFEIFPKES SWPNHTTTGV SASCSHNGES SFYKNLLWLT G KNGLYPNL ...String: ADPGYLLEDT ICIGYHANNS TDTVDTVLEK NVTVTHSVNL LEDSHNGKLC LLKGIAPLQL GNCSVAGWIL GNPECELLIS RESWSYIVE KPNPENGTCY PGHFADYEEL REQLSSVSSF ERFEIFPKES SWPNHTTTGV SASCSHNGES SFYKNLLWLT G KNGLYPNL SKSYANNKEK EVLVLWGVHH PPNIGDQRAL YHTENAYVSV VSSHYSRKFT PEIAKRPKVR DQEGRINYYW TL LEPGDTI IFEANGNLIA PRYAFALSRG FGSGIINSNA PMDECDAKCQ TPQGAINSSL PFQNVHPVTI GECPKYVRSA KLR MVTGLR NIPSIQSRGL FGAIAGFIEG GWTGMVDGWY GYHHQNEQGS GYAADQKSTQ NAINGITNKV NSVIEKMNTQ FTAV GKEFN KLERRMENLN KKVDDGFIDI WTYNAELLVL LENERTLDFH DSNVKNLYEK VKSQLKNNAK EIGNGCFEFY HKCND ECME SVKNGTYDYP KYSEESKLNR EKIDGVRSGS GGALEVLFQ |
-Macromolecule #2: ab109 Fab heavy chain
Macromolecule | Name: ab109 Fab heavy chain / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 23.267232 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: QVQLVQSGAE VKKPGASVKV SCKASGYTFT GYYIHWVRQA PGQGLEWMGW INPNTGGTVY AQTFQARVTM TRDTSISTAY MELIRLRSD DTAVYYCARE RGTGAPDAFN IWGQGTLVTV SGASTKGPSV FPLAPSGTAA LGCLVKDYFP EPVTVSWNSG A LTSGVHTF ...String: QVQLVQSGAE VKKPGASVKV SCKASGYTFT GYYIHWVRQA PGQGLEWMGW INPNTGGTVY AQTFQARVTM TRDTSISTAY MELIRLRSD DTAVYYCARE RGTGAPDAFN IWGQGTLVTV SGASTKGPSV FPLAPSGTAA LGCLVKDYFP EPVTVSWNSG A LTSGVHTF PAVLQSSGLY SLSSVVTVPS SSLGTQTYIC NVNHKPSNTK VDKKVEPKSC |
-Macromolecule #3: ab109 Fab light chain
Macromolecule | Name: ab109 Fab light chain / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 23.806414 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: DIVMTQSPAS LAVSLGQRAT ISCRASKSVS TSGYSYIHWY QQKPGQPPKL LIYLATNLES GVPARFSGSG SGTDFTLNIH PVEEEDAAT YYCQHSRDTP YTFGGGTKLE IKRTVAAPSV FIFPPSDEQL KSGTASVVCL LNNFYPREAK VQWKVDNALQ S GNSQESVT ...String: DIVMTQSPAS LAVSLGQRAT ISCRASKSVS TSGYSYIHWY QQKPGQPPKL LIYLATNLES GVPARFSGSG SGTDFTLNIH PVEEEDAAT YYCQHSRDTP YTFGGGTKLE IKRTVAAPSV FIFPPSDEQL KSGTASVVCL LNNFYPREAK VQWKVDNALQ S GNSQESVT EQDSKDSTYS LSSTLTLSKA DYEKHKVYAC EVTHQGLSSP VTKSFNRGEC |
-Macromolecule #5: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 5 / Number of copies: 6 / 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 BIOQUANTUM (6k x 4k) / Average electron dose: 1.07 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |