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- EMDB-46046: Cryo-EM structure of FNI9 IgG in complex with influenza virus neu... -
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Open data
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Basic information
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Title | Cryo-EM structure of FNI9 IgG in complex with influenza virus neuraminidase from A/Kansas/14/2017 (H3N2) | |||||||||
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![]() | Neuraminidase / Hydrolase / Antibody complex / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex | |||||||||
Function / homology | ![]() exo-alpha-sialidase / exo-alpha-sialidase activity / viral budding from plasma membrane / carbohydrate metabolic process / host cell plasma membrane / virion membrane / metal ion binding / membrane Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.97 Å | |||||||||
![]() | Jo G / Han J / Torres JL / Ferguson JA / Ward AB | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural basis of broad protection against influenza virus by human antibodies targeting the neuraminidase active site via a recurring motif in CDR H3. Authors: Gyunghee Jo / Seiya Yamayoshi / Krystal M Ma / Olivia Swanson / Jonathan L Torres / James A Ferguson / Monica L Fernández-Quintero / Jiachen Huang / Jeffrey Copps / Alesandra J Rodriguez / ...Authors: Gyunghee Jo / Seiya Yamayoshi / Krystal M Ma / Olivia Swanson / Jonathan L Torres / James A Ferguson / Monica L Fernández-Quintero / Jiachen Huang / Jeffrey Copps / Alesandra J Rodriguez / Jon M Steichen / Yoshihiro Kawaoka / Julianna Han / Andrew B Ward / ![]() ![]() Abstract: Influenza viruses evolve rapidly, driving seasonal epidemics and posing global pandemic threats. While neuraminidase (NA) has emerged as a vaccine target, shared molecular features of NA antibody ...Influenza viruses evolve rapidly, driving seasonal epidemics and posing global pandemic threats. While neuraminidase (NA) has emerged as a vaccine target, shared molecular features of NA antibody responses are still not well understood. Here, we describe cryo-electron microscopy structures of the broadly protective human antibody DA03E17, which was previously identified from an H1N1-infected donor, in complex with NA from A/H1N1, A/H3N2, and B/Victoria-lineage viruses. DA03E17 targets the highly conserved NA active site using its long CDR H3, which features a DR (Asp-Arg) motif that engages catalytic residues and mimics sialic acid interactions. We further demonstrate that this motif is conserved among several NA active site-targeting antibodies, indicating a common receptor mimicry strategy. We also identified BCR sequences containing this DR motif across all donors in a healthy human repertoire database, suggesting that such precursors may be relatively common and have vaccine targeting potential. Our findings reveal shared molecular features in NA active site-targeting antibodies that can be harnessed to design broad, immune-focused influenza vaccines. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 483.6 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 19.2 KB 19.2 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 16.9 KB | Display | ![]() |
Images | ![]() | 94 KB | ||
Masks | ![]() | 512 MB | ![]() | |
Filedesc metadata | ![]() | 6.8 KB | ||
Others | ![]() ![]() | 475.7 MB 475.7 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 1.2 MB | Display | ![]() |
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Full document | ![]() | 1.2 MB | Display | |
Data in XML | ![]() | 26.6 KB | Display | |
Data in CIF | ![]() | 34.6 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 9cyjMC ![]() 9cyeC ![]() 9cyfC ![]() 9cygC ![]() 9cyhC ![]() 9cyiC ![]() 9o4nC ![]() 9o4oC ![]() 9o4pC ![]() 9o4qC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.725 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
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Density Histograms |
-Half map: #1
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Density Histograms |
-Half map: #2
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Density Histograms |
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Sample components
-Entire : FNI9 IgG in complex with influenza virus neuraminidase from A/Kan...
Entire | Name: FNI9 IgG in complex with influenza virus neuraminidase from A/Kansas/14/2017 (H3N2) |
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Components |
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-Supramolecule #1: FNI9 IgG in complex with influenza virus neuraminidase from A/Kan...
Supramolecule | Name: FNI9 IgG in complex with influenza virus neuraminidase from A/Kansas/14/2017 (H3N2) type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: Neuraminidase
Macromolecule | Name: Neuraminidase / type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO / EC number: exo-alpha-sialidase |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 52.145516 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MDAMKRGLCC VLLLCGAVFV SPHHHHHHGS SSSDYSDLQR VKQELLEEVK KELQKVKEEI IEAFVQELRK RGSENLYFQS GSEYRNWSK PQCGITGFAP FSKDNSIRLS AGGDIWVTRE PYVSCDPDKC YQFALGQGTT INNVHSNNTA RDRTPHRTLL M NELGVPFH ...String: MDAMKRGLCC VLLLCGAVFV SPHHHHHHGS SSSDYSDLQR VKQELLEEVK KELQKVKEEI IEAFVQELRK RGSENLYFQS GSEYRNWSK PQCGITGFAP FSKDNSIRLS AGGDIWVTRE PYVSCDPDKC YQFALGQGTT INNVHSNNTA RDRTPHRTLL M NELGVPFH LGTKQVCIAW SSSSCHDGKA WLHVCITGDD KNATASFIYN GRLVDSVVSW SKDILRTQES ECVCINGTCT VV MTDGNAT GKADTKILFI EEGKIVHTSK LSGSAQHVEE CSCYPRYPGV RCVCRDNWKG SNRPIVDINI KDHSIVSSYV CSG LVGDTP RKTDSSSSSH CLNPNNEKGG HGVKGWAFDD GNDVWMGRTI NETSRLGYET FKVVEGWSNP KSKLQINRQV IVDR GDRSG YSGIFSVEGK SCINRCFYVE LIRGRKEETE VLWTSNSIVV FCGTSGTYGT GSWPDGADLN LMHI UniProtKB: Neuraminidase |
-Macromolecule #2: FNI9 IgG heavy chain
Macromolecule | Name: FNI9 IgG heavy chain / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 24.418053 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: QVHLVQSGAE VKEPGSSVTV SCKASGGSFN NQAISWVRQA PGQGLEWMGG IFPISGTPTS AQRFQGRVTF TADESTTTVY MDLSSLRSD DTAVYYCARA GSDYFNRDLG WENYYFASWG QGTLVTVSSA STKGPSVFPL APSSKSTSGG TAALGCLVKD Y FPEPVTVS ...String: QVHLVQSGAE VKEPGSSVTV SCKASGGSFN NQAISWVRQA PGQGLEWMGG IFPISGTPTS AQRFQGRVTF TADESTTTVY MDLSSLRSD DTAVYYCARA GSDYFNRDLG WENYYFASWG QGTLVTVSSA STKGPSVFPL APSSKSTSGG TAALGCLVKD Y FPEPVTVS WNSGALTSGV HTFPAVLQSS GLYSLSSVVT VPSSSLGTQT YICNVNHKPS NTKVDKKVEP KSC |
-Macromolecule #3: FNI9 IgG light chain
Macromolecule | Name: FNI9 IgG light chain / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 23.565068 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: EIVMTQSPAT LSLSSGERAT LSCRASRSVS SNLAWYQQKP GQAPRLLIYD ASTRATGFSA RFAGSGSGTE FTLTISSLQS EDSAIYYCQ QYNNWPPWTF GQGTKVEIKR TVAAPSVFIF PPSDEQLKSG TASVVCLLNN FYPREAKVQW KVDNALQSGN S QESVTEQD ...String: EIVMTQSPAT LSLSSGERAT LSCRASRSVS SNLAWYQQKP GQAPRLLIYD ASTRATGFSA RFAGSGSGTE FTLTISSLQS EDSAIYYCQ QYNNWPPWTF GQGTKVEIKR TVAAPSVFIF PPSDEQLKSG TASVVCLLNN FYPREAKVQW KVDNALQSGN S QESVTEQD SKDSTYSLSS TLTLSKADYE KHKVYACEVT HQGLSSPVTK SFNRGEC |
-Macromolecule #8: CALCIUM ION
Macromolecule | Name: CALCIUM ION / type: ligand / ID: 8 / Number of copies: 4 / Formula: CA |
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Molecular weight | Theoretical: 40.078 Da |
-Macromolecule #9: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 9 / Number of copies: 8 / 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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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE / Instrument: FEI VITROBOT MARK IV |
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Electron microscopy
Microscope | TFS GLACIOS |
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Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 45.0 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.4000000000000001 µm / Nominal defocus min: 0.7000000000000001 µm / Nominal magnification: 190000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |