[English] 日本語

- EMDB-41826: A mechanistic understanding of protective influenza B neuraminida... -
+
Open data
-
Basic information
Entry | ![]() | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | A mechanistic understanding of protective influenza B neuraminidase mAbs at the airway interface | |||||||||
![]() | ||||||||||
![]() |
| |||||||||
![]() | Neuraminidase Sialidase / HYDROLASE | |||||||||
Function / homology | ![]() exo-alpha-sialidase / exo-alpha-sialidase activity / 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: 3.21 Å | |||||||||
![]() | Ferguson JA / Raghavan SSR / Ward AB | |||||||||
Funding support | ![]()
| |||||||||
![]() | ![]() Title: Isolation of human antibodies against influenza B neuraminidase and mechanisms of protection at the airway interface. Authors: Rachael M Wolters / James A Ferguson / Ivette A Nuñez / Elaine E Chen / Ty Sornberger / Luke Myers / Svearike Oeverdieck / Sai Sundar Rajan Raghavan / Chandrahaas Kona / Laura S Handal / ...Authors: Rachael M Wolters / James A Ferguson / Ivette A Nuñez / Elaine E Chen / Ty Sornberger / Luke Myers / Svearike Oeverdieck / Sai Sundar Rajan Raghavan / Chandrahaas Kona / Laura S Handal / Trevor E Esilu / Edgar Davidson / Benjamin J Doranz / Taylor B Engdahl / Nurgun Kose / Lauren E Williamson / C Buddy Creech / Katherine N Gibson-Corley / Andrew B Ward / James E Crowe / ![]() Abstract: Influenza B viruses (IBVs) comprise a substantial portion of the circulating seasonal human influenza viruses. Here, we describe the isolation of human monoclonal antibodies (mAbs) that recognized ...Influenza B viruses (IBVs) comprise a substantial portion of the circulating seasonal human influenza viruses. Here, we describe the isolation of human monoclonal antibodies (mAbs) that recognized the IBV neuraminidase (NA) glycoprotein from an individual following seasonal vaccination. Competition-binding experiments suggested the antibodies recognized two major antigenic sites. One group, which included mAb FluB-393, broadly inhibited IBV NA sialidase activity, protected prophylactically in vivo, and bound to the lateral corner of NA. The second group contained an active site mAb, FluB-400, that broadly inhibited IBV NA sialidase activity and virus replication in vitro in primary human respiratory epithelial cell cultures and protected against IBV in vivo when administered systemically or intranasally. Overall, the findings described here shape our mechanistic understanding of the human immune response to the IBV NA glycoprotein through the demonstration of two mAb delivery routes for protection against IBV and the identification of potential IBV therapeutic candidates. | |||||||||
History |
|
-
Structure visualization
Supplemental images |
---|
-
Downloads & links
-EMDB archive
Map data | ![]() | 166.7 MB | ![]() | |
---|---|---|---|---|
Header (meta data) | ![]() ![]() | 22.4 KB 22.4 KB | Display Display | ![]() |
Images | ![]() | 62.7 KB | ||
Filedesc metadata | ![]() | 7.2 KB | ||
Others | ![]() ![]() | 25.1 MB 25.1 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 763.7 KB | Display | ![]() |
---|---|---|---|---|
Full document | ![]() | 763.3 KB | Display | |
Data in XML | ![]() | 14.7 KB | Display | |
Data in CIF | ![]() | 17.5 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8u1sMC ![]() 8u1cC ![]() 8u1qC M: atomic model generated by this map C: citing same article ( |
---|---|
Similar structure data | Similarity search - Function & homology ![]() |
-
Links
EMDB pages | ![]() ![]() |
---|---|
Related items in Molecule of the Month |
-
Map
File | ![]() | ||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.725 Å | ||||||||||||||||||||||||||||||||||||
Density |
| ||||||||||||||||||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
|
-Supplemental data
-Half map: #2
File | emd_41826_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: #1
File | emd_41826_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-
Sample components
-Entire : Complex of human donor mAb-fv domain bound to influenza B neurami...
Entire | Name: Complex of human donor mAb-fv domain bound to influenza B neuraminidase |
---|---|
Components |
|
-Supramolecule #1: Complex of human donor mAb-fv domain bound to influenza B neurami...
Supramolecule | Name: Complex of human donor mAb-fv domain bound to influenza B neuraminidase type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 |
---|---|
Source (natural) | Organism: ![]() |
-Macromolecule #1: Neuraminidase
Macromolecule | Name: Neuraminidase / type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 51.104258 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MLPSTIQTLT LFLTSGGVLL SLYVSASLSY LLYSDILLKF SPTEITAPTM PLDCANASNV QAVNRSATKG VTLLLPGPEW TYPRLSCPG STFQKALLIS PHRFGETKGN SAPLIIREPF VACGPNECKH FALTHYAAQP GGYYNGTRGD RNKLRHLISV K LGKIPTVE ...String: MLPSTIQTLT LFLTSGGVLL SLYVSASLSY LLYSDILLKF SPTEITAPTM PLDCANASNV QAVNRSATKG VTLLLPGPEW TYPRLSCPG STFQKALLIS PHRFGETKGN SAPLIIREPF VACGPNECKH FALTHYAAQP GGYYNGTRGD RNKLRHLISV K LGKIPTVE NSIFHMAAWS GSACHDGKEW TYIGVDGPDN NALLKVKYGE AYTDTYHSYA NNILRTQESA CNCIGGNCYL MI TDGSASG VSECRFLKIR EGRIIKEIFP TGRVKHTEEC TCGFASNKTI ECACRDNRYT AKRPFVKLNV ETDTAEIRLM CTD TYLDTP RPNDGSITGP CESDGDKGSG GIKGGFVHQR MKSKIGRWYS RTMSKTERMG MGLYVKYGGD PWADSDALAF SGVM VPMKE PGWYSFGFEI KDKKCDVPCI GIEMVHDGGK ETWHSAATAI YCLMGSGQLL WDTVTGVDMA L UniProtKB: Neuraminidase |
-Macromolecule #2: mAb-393 heavy chain
Macromolecule | Name: mAb-393 heavy chain / type: protein_or_peptide / ID: 2 / Number of copies: 4 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 13.650218 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: QVQLQEAGPG LVKPSETLSL TCTVSGGSVS DTSYFWGWIR QPPGKGLEWI GSVSYTGDNY YNPSLRSRVA ISLDAPKNRF SLKLRSVTA ADTAVYYCAR RPTHFDFWKT FDYWGQGSLV TVSS |
-Macromolecule #3: mAb-393 light chain
Macromolecule | Name: mAb-393 light chain / type: protein_or_peptide / ID: 3 / Number of copies: 4 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 11.812088 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: DIQMTQSPST LSASVGDRVT ITCRASQSIS TWLAWYQQKP GEAPKLLIYK ASNLESGVPS RFSGSGSGTE FTLTISSLQP DDFATYYCQ QYNIYSWTFG QGTKVEIK |
-Macromolecule #4: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 4 / Number of copies: 4 / Formula: NAG |
---|---|
Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ![]() ChemComp-NAG: |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
![]() | single particle reconstruction |
Aggregation state | particle |
-
Sample preparation
Concentration | 0.4 mg/mL |
---|---|
Buffer | pH: 7.4 / Details: TBS |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 298 K / Instrument: FEI VITROBOT MARK III |
-
Electron microscopy
Microscope | FEI TALOS ARCTICA |
---|---|
Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Digitization - Dimensions - Width: 4048 pixel / Digitization - Dimensions - Height: 4048 pixel / Number grids imaged: 1 / Number real images: 6177 / Average electron dose: 49.87 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: ![]() |
Electron optics | C2 aperture diameter: 100.0 µm / Calibrated defocus max: 1.5 µm / Calibrated defocus min: 1.5 µm / Calibrated magnification: 190000 / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 0.7000000000000001 µm / Nominal defocus min: 0.7000000000000001 µm / Nominal magnification: 190000 |
Sample stage | Specimen holder model: OTHER / Cooling holder cryogen: NITROGEN |
Experimental equipment | ![]() Model: Talos Arctica / Image courtesy: FEI Company |
+
Image processing
-Atomic model buiding 1
Initial model |
| ||||||
---|---|---|---|---|---|---|---|
Output model | ![]() PDB-8u1s: |