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Yorodumi- EMDB-21043: Structure of human 2E01 Fab in complex with influenza virus neura... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-21043 | |||||||||
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Title | Structure of human 2E01 Fab in complex with influenza virus neuraminidase from B/Phuket/3073/2013 | |||||||||
Map data | ||||||||||
Sample |
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Function / homology | Function and homology information exo-alpha-(2->3)-sialidase activity / exo-alpha-(2->6)-sialidase activity / exo-alpha-(2->8)-sialidase activity / exo-alpha-sialidase / carbohydrate metabolic process / host cell plasma membrane / virion membrane / membrane / metal ion binding Similarity search - Function | |||||||||
Biological species | Influenza B virus / Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.8 Å | |||||||||
Authors | Dai YN / Fremont DH / Center for Structural Genomics of Infectious Diseases (CSGID) | |||||||||
Citation | Journal: Immunity / Year: 2020 Title: Human Antibodies Targeting Influenza B Virus Neuraminidase Active Site Are Broadly Protective. Authors: Anders Madsen / Ya-Nan Dai / Meagan McMahon / Aaron J Schmitz / Jackson S Turner / Jessica Tan / Tingting Lei / Wafaa B Alsoussi / Shirin Strohmeier / Mostafa Amor / Bassem M Mohammed / ...Authors: Anders Madsen / Ya-Nan Dai / Meagan McMahon / Aaron J Schmitz / Jackson S Turner / Jessica Tan / Tingting Lei / Wafaa B Alsoussi / Shirin Strohmeier / Mostafa Amor / Bassem M Mohammed / Philip A Mudd / Viviana Simon / Rebecca J Cox / Daved H Fremont / Florian Krammer / Ali H Ellebedy / Abstract: Influenza B virus (IBV) infections can cause severe disease in children and the elderly. Commonly used antivirals have lower clinical effectiveness against IBV compared to influenza A viruses (IAV). ...Influenza B virus (IBV) infections can cause severe disease in children and the elderly. Commonly used antivirals have lower clinical effectiveness against IBV compared to influenza A viruses (IAV). Neuraminidase (NA), the second major surface protein on the influenza virus, is emerging as a target of broadly protective antibodies that recognize the NA active site of IAVs. However, similarly broadly protective antibodies against IBV NA have not been identified. Here, we isolated and characterized human monoclonal antibodies (mAbs) that target IBV NA from an IBV-infected patient. Two mAbs displayed broad and potent capacity to inhibit IBV NA enzymatic activity, neutralize the virus in vitro, and protect against lethal IBV infection in mice in prophylactic and therapeutic settings. These mAbs inserted long CDR-H3 loops into the NA active site, engaging residues highly conserved among IBV NAs. These mAbs provide a blueprint for the development of improved vaccines and therapeutics against IBVs. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_21043.map.gz | 55.2 MB | EMDB map data format | |
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Header (meta data) | emd-21043-v30.xml emd-21043.xml | 15.9 KB 15.9 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_21043_fsc.xml | 8.8 KB | Display | FSC data file |
Images | emd_21043.png | 26.6 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-21043 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-21043 | HTTPS FTP |
-Validation report
Summary document | emd_21043_validation.pdf.gz | 500.5 KB | Display | EMDB validaton report |
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Full document | emd_21043_full_validation.pdf.gz | 500.1 KB | Display | |
Data in XML | emd_21043_validation.xml.gz | 10.3 KB | Display | |
Data in CIF | emd_21043_validation.cif.gz | 13.5 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-21043 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-21043 | HTTPS FTP |
-Related structure data
Related structure data | 6v4oMC 6v4nC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_21043.map.gz / Format: CCP4 / Size: 59.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Voxel size | X=Y=Z: 1.1 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : Structure of human 2E01 Fab in complex with influenza virus neura...
Entire | Name: Structure of human 2E01 Fab in complex with influenza virus neuraminidase from B/Phuket/3073/2013 |
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Components |
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-Supramolecule #1: Structure of human 2E01 Fab in complex with influenza virus neura...
Supramolecule | Name: Structure of human 2E01 Fab in complex with influenza virus neuraminidase from B/Phuket/3073/2013 type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 |
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Molecular weight | Theoretical: 400 KDa |
-Supramolecule #2: Influenza virus neuraminidase
Supramolecule | Name: Influenza virus neuraminidase / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: Influenza B virus / Strain: B/Phuket/3073/2013 |
Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
-Supramolecule #3: Human antibody
Supramolecule | Name: Human antibody / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2-#3 |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Homo sapiens (human) |
-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: Influenza B virus |
Molecular weight | Theoretical: 50.038824 KDa |
Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
Sequence | String: ADPHHHHHHS SSDYSDLQRV KQELLEEVKK ELQKVKEEII EAFVQELRKR GSLVPRGSPS RWTYPRLSCP GSTFQKALLI SPHRFGETK GNSAPLIIRE PFIACGPKEC KHFALTHYAA QPGGYYNGTR EDRNKLRHLI SVKLGKIPTV ENSIFHMAAW S GSACHDGR ...String: ADPHHHHHHS SSDYSDLQRV KQELLEEVKK ELQKVKEEII EAFVQELRKR GSLVPRGSPS RWTYPRLSCP GSTFQKALLI SPHRFGETK GNSAPLIIRE PFIACGPKEC KHFALTHYAA QPGGYYNGTR EDRNKLRHLI SVKLGKIPTV ENSIFHMAAW S GSACHDGR EWTYIGVDGP DSNALLKIKY GEAYTDTYHS YAKNILRTQE SACNCIGGDC YLMITDGPAS GISECRFLKI RE GRIIKEI FPTGRVKHTE ECTCGFASNK TIECACRDNS YTAKRPFVKL NVETDTAEIR LMCTKTYLDT PRPNDGSITG PCE SDGDEG SGGIKGGFVH QRMASKIGRW YSRTMSKTKR MGMGLYVKYD GDPWTDSEAL ALSGVMVSME EPGWYSFGFE IKDK KCDVP CIGIEMVHDG GKTTWHSAAT AIYCLMGSGQ LLWDTVTGVN MTL |
-Macromolecule #2: Antibody Fab heavy chain
Macromolecule | Name: Antibody Fab heavy chain / type: protein_or_peptide / ID: 2 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 26.840137 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: EVQLVQSGAE VKKPGSSVKV SCKASGYTFI NHALSWVRQA PGQGLEWVGG IIPIFGLAKY GQKFQDRVTI TADESTKTAY MDLRSLRSD DTAVYYCARD TVAVYEDFDW SSPYFFYMDV WGKGTTVTVS SASTKGPSVF PLAPSSKSTS GGTAALGCLV K DYFPEPVT ...String: EVQLVQSGAE VKKPGSSVKV SCKASGYTFI NHALSWVRQA PGQGLEWVGG IIPIFGLAKY GQKFQDRVTI TADESTKTAY MDLRSLRSD DTAVYYCARD TVAVYEDFDW SSPYFFYMDV WGKGTTVTVS SASTKGPSVF PLAPSSKSTS GGTAALGCLV K DYFPEPVT VSWNSGALTS GVHTFPAVLQ SSGLYSLSSV VTVPSSSLGT QTYICNVNHK PSNTKVDKKV EPKSCRSLVP RG SSGHHHH HH |
-Macromolecule #3: Antibody Fab light chain
Macromolecule | Name: Antibody Fab light chain / type: protein_or_peptide / ID: 3 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 23.327992 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: EIVLTQSPAT LSLFPGERAT LSCRASQSAG SKSLAWYQHK VGQPPRLLIN GASSRATGIP DRFSGSGSGP DFNLTISRLE PEDFAVYYC QRYGTSLVTF GGGTKVEIKR TVAAPSVFIF PPSDEQLKSG TASVVCLLNN FYPREAKVQW KVDNALQSGN S QESVTEQD ...String: EIVLTQSPAT LSLFPGERAT LSCRASQSAG SKSLAWYQHK VGQPPRLLIN GASSRATGIP DRFSGSGSGP DFNLTISRLE PEDFAVYYC QRYGTSLVTF GGGTKVEIKR TVAAPSVFIF PPSDEQLKSG TASVVCLLNN FYPREAKVQW KVDNALQSGN S QESVTEQD SKDSTYSLSS TLTLSKADYE KHKVYACEVT HQGLSSPVTK SFNRGEC |
-Macromolecule #5: beta-D-mannopyranose
Macromolecule | Name: beta-D-mannopyranose / type: ligand / ID: 5 / Number of copies: 4 / Formula: BMA |
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Molecular weight | Theoretical: 180.156 Da |
Chemical component information | ChemComp-BMA: |
-Macromolecule #6: CALCIUM ION
Macromolecule | Name: CALCIUM ION / type: ligand / ID: 6 / Number of copies: 4 / Formula: CA |
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Molecular weight | Theoretical: 40.078 Da |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 0.15 mg/mL |
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Buffer | pH: 7.4 |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Average electron dose: 66.0 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 |