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- EMDB-29686: N2 neuraminidase of A/Tanzania/205/2010 H3N2 in complex with 4 FN... -
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Open data
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Basic information
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Title | N2 neuraminidase of A/Tanzania/205/2010 H3N2 in complex with 4 FNI19 Fab molecules | |||||||||
![]() | 4 FNI19 Fabs in complex with tetrameric N2 NA protein from A/Tanzania/2010 strain | |||||||||
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![]() | viral glycoprotein / antibody / Fab / influenza / virus / VIRAL PROTEIN-IMMUNE SYSTEM complex | |||||||||
Function / homology | ![]() exo-alpha-(2->3)-sialidase activity / exo-alpha-(2->6)-sialidase activity / exo-alpha-(2->8)-sialidase activity / exo-alpha-sialidase / viral budding from plasma membrane / carbohydrate metabolic process / host cell plasma membrane / virion membrane / membrane / metal ion binding Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.1 Å | |||||||||
![]() | Dang HV / Snell G | |||||||||
Funding support | ![]()
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![]() | ![]() Title: A pan-influenza antibody inhibiting neuraminidase via receptor mimicry. Authors: Corey Momont / Ha V Dang / Fabrizia Zatta / Kevin Hauser / Caihong Wang / Julia di Iulio / Andrea Minola / Nadine Czudnochowski / Anna De Marco / Kaitlin Branch / David Donermeyer / Siddhant ...Authors: Corey Momont / Ha V Dang / Fabrizia Zatta / Kevin Hauser / Caihong Wang / Julia di Iulio / Andrea Minola / Nadine Czudnochowski / Anna De Marco / Kaitlin Branch / David Donermeyer / Siddhant Vyas / Alex Chen / Elena Ferri / Barbara Guarino / Abigail E Powell / Roberto Spreafico / Samantha S Yim / Dale R Balce / Istvan Bartha / Marcel Meury / Tristan I Croll / David M Belnap / Michael A Schmid / William Timothy Schaiff / Jessica L Miller / Elisabetta Cameroni / Amalio Telenti / Herbert W Virgin / Laura E Rosen / Lisa A Purcell / Antonio Lanzavecchia / Gyorgy Snell / Davide Corti / Matteo Samuele Pizzuto / ![]() ![]() ![]() Abstract: Rapidly evolving influenza A viruses (IAVs) and influenza B viruses (IBVs) are major causes of recurrent lower respiratory tract infections. Current influenza vaccines elicit antibodies ...Rapidly evolving influenza A viruses (IAVs) and influenza B viruses (IBVs) are major causes of recurrent lower respiratory tract infections. Current influenza vaccines elicit antibodies predominantly to the highly variable head region of haemagglutinin and their effectiveness is limited by viral drift and suboptimal immune responses. Here we describe a neuraminidase-targeting monoclonal antibody, FNI9, that potently inhibits the enzymatic activity of all group 1 and group 2 IAVs, as well as Victoria/2/87-like, Yamagata/16/88-like and ancestral IBVs. FNI9 broadly neutralizes seasonal IAVs and IBVs, including the immune-evading H3N2 strains bearing an N-glycan at position 245, and shows synergistic activity when combined with anti-haemagglutinin stem-directed antibodies. Structural analysis reveals that D107 in the FNI9 heavy chain complementarity-determinant region 3 mimics the interaction of the sialic acid carboxyl group with the three highly conserved arginine residues (R118, R292 and R371) of the neuraminidase catalytic site. FNI9 demonstrates potent prophylactic activity against lethal IAV and IBV infections in mice. The unprecedented breadth and potency of the FNI9 monoclonal antibody supports its development for the prevention of influenza illness by seasonal and pandemic viruses. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 62.3 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 19.7 KB 19.7 KB | Display Display | ![]() |
Images | ![]() | 87.7 KB | ||
Others | ![]() ![]() | 115.9 MB 115.9 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8g30MC ![]() 8g3mC ![]() 8g3nC ![]() 8g3oC ![]() 8g3pC ![]() 8g3qC ![]() 8g3rC ![]() 8g3vC ![]() 8g3zC ![]() 8g40C 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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Annotation | 4 FNI19 Fabs in complex with tetrameric N2 NA protein from A/Tanzania/2010 strain | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.927 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #1
File | emd_29686_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_29686_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
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Sample components
-Entire : N2 neuraminidase of A/Tanzania/205/2010 H3N2 in complex with 4 FN...
Entire | Name: N2 neuraminidase of A/Tanzania/205/2010 H3N2 in complex with 4 FNI19 Fab molecules |
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Components |
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-Supramolecule #1: N2 neuraminidase of A/Tanzania/205/2010 H3N2 in complex with 4 FN...
Supramolecule | Name: N2 neuraminidase of A/Tanzania/205/2010 H3N2 in complex with 4 FNI19 Fab molecules type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 Details: Fab fragment generated by proteolytic cleavage of FNI19 IgG1 antibody |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 0.42 kDa/nm |
-Macromolecule #1: FNI19 Fab heavy chain
Macromolecule | Name: FNI19 Fab heavy chain / type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 24.692602 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: QVQLVQSGAE VKRPGSSVRV SCKASEGTFN KYTLTWVRQA PGQGLEWMGG IIPISGIANY AQKFQGRVAI TADESTTTAY MELSSLRSE DSAVYYCATA VSDYFNRDLG WEDYYFPFWG QGTLVTVASA STKGPSVFPL APSSKSTSGG TAALGCLVKD Y FPEPVTVS ...String: QVQLVQSGAE VKRPGSSVRV SCKASEGTFN KYTLTWVRQA PGQGLEWMGG IIPISGIANY AQKFQGRVAI TADESTTTAY MELSSLRSE DSAVYYCATA VSDYFNRDLG WEDYYFPFWG QGTLVTVASA STKGPSVFPL APSSKSTSGG TAALGCLVKD Y FPEPVTVS WNSGALTSGV HTFPAVLQSS GLYSLSSVVT VPSSSLGTQT YICNVNHKPS NTKVDKRVEP KSC |
-Macromolecule #2: FNI19 Fab light chain
Macromolecule | Name: FNI19 Fab light chain / type: protein_or_peptide / ID: 2 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 23.549264 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: EIVMTQSPAT LSVSPGARAT LFCRASRSVS DNLAWYQQKP GQAPRLLIFG ASTRATGVPA RFSGSGSGTQ FTLTISSLQS EDFAVYYCQ HYNIWPPWTF GQGTKVEIKR TVAAPSVFIF PPSDEQLKSG TASVVCLLNN FYPREAKVQW KVDNALQSGN S QESVTEQD ...String: EIVMTQSPAT LSVSPGARAT LFCRASRSVS DNLAWYQQKP GQAPRLLIFG ASTRATGVPA RFSGSGSGTQ FTLTISSLQS EDFAVYYCQ HYNIWPPWTF GQGTKVEIKR TVAAPSVFIF PPSDEQLKSG TASVVCLLNN FYPREAKVQW KVDNALQSGN S QESVTEQD SKDSTYSLSS TLTLSKADYE KHKVYACEVT HQGLSSPVTK SFNRGEC |
-Macromolecule #3: Neuraminidase
Macromolecule | Name: Neuraminidase / type: protein_or_peptide / ID: 3 / Details: A/Tanzania/205/2010 H3N2 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 54.755047 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: METDTLLLWV LLLWVPGSTG DHHHHHHGSG LNDIFEAQKI EWHEGSIINE TADDIVYRLT VIIDDRYESL KNLITLRADR LEMIINDNV STILASGENL YFQGSAEYRN WSKPQCDITG FAPFSKDNSI RLSAGGDIWV TREPYVSCDP DKCYQFALGQ G TTLNNVHS ...String: METDTLLLWV LLLWVPGSTG DHHHHHHGSG LNDIFEAQKI EWHEGSIINE TADDIVYRLT VIIDDRYESL KNLITLRADR LEMIINDNV STILASGENL YFQGSAEYRN WSKPQCDITG FAPFSKDNSI RLSAGGDIWV TREPYVSCDP DKCYQFALGQ G TTLNNVHS NNTVRDRTPY RTLLMNELGV PFHLGTKQVC IAWSSSSCHD GKAWLHVCIT GDDKNATASF IYNGRLVDSV VS WSKEILR TQESECVCIN GTCTVVMTDG SASGKADTKI LFIEEGKIVH TSTLSGSAQH VEECSCYPRY PGVRCVCRDN WKG SNRPIV DINIKDHSIV SSYVCSGLVG DTPRKNDSSS SSHCLDPNNE EGGHGVKGWA FDDGNDVWMG RTINETSRLG YETF KVIEG WSNPKSKLQI NRQVIVDRGN RSGYSGIFSV EGKSCINRCF YVELIRGRKE ETEVLWTSNS IVVFCGTSGT YGTGS WPDG ADLNLMPI |
-Macromolecule #8: CALCIUM ION
Macromolecule | Name: CALCIUM ION / type: ligand / ID: 8 / Number of copies: 5 / Formula: CA |
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Molecular weight | Theoretical: 40.078 Da |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 0.2 mg/mL | ||||||||||||
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Buffer | pH: 8 Component:
Details: 50 mM Tris-HCl, 150 mM NaCl, 10 mM CaCl2, pH 8.0 | ||||||||||||
Grid | Model: UltrAuFoil R1.2/1.3 / Material: GOLD / Pretreatment - Type: GLOW DISCHARGE | ||||||||||||
Vitrification | Cryogen name: ETHANE |
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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: 19.35 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.5 µm |
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Image processing
Startup model | Type of model: OTHER / Details: ab initio |
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Final reconstruction | Applied symmetry - Point group: C4 (4 fold cyclic) / Resolution.type: BY AUTHOR / Resolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 170901 |
Initial angle assignment | Type: PROJECTION MATCHING |
Final angle assignment | Type: PROJECTION MATCHING |