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- EMDB-6793: Cryo-EM structure of zika virus complexed with Fab of ZKA190 at p... -
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Basic information
Entry | Database: EMDB / ID: EMD-6793 | |||||||||
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Title | Cryo-EM structure of zika virus complexed with Fab of ZKA190 at pH 8.0 and 37 celsius degree | |||||||||
![]() | Zika virus complexed with the Fab molecule of a human monoclonal antibody named ZKA190 | |||||||||
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![]() | virus / antibody / complex / VIRUS-IMMUNE SYSTEM complex / icosahedral virus | |||||||||
Function / homology | ![]() symbiont-mediated suppression of host JAK-STAT cascade via inhibition of host TYK2 activity / flavivirin / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT2 activity / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT1 activity / negative regulation of innate immune response / methyltransferase activity / viral capsid / double-stranded RNA binding / nucleoside-triphosphate phosphatase / 4 iron, 4 sulfur cluster binding ...symbiont-mediated suppression of host JAK-STAT cascade via inhibition of host TYK2 activity / flavivirin / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT2 activity / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT1 activity / negative regulation of innate immune response / methyltransferase activity / viral capsid / double-stranded RNA binding / nucleoside-triphosphate phosphatase / 4 iron, 4 sulfur cluster binding / mRNA (guanine-N7)-methyltransferase / methyltransferase cap1 / clathrin-dependent endocytosis of virus by host cell / methylation / mRNA (nucleoside-2'-O-)-methyltransferase activity / mRNA 5'-cap (guanine-N7-)-methyltransferase activity / membrane => GO:0016020 / molecular adaptor activity / RNA helicase activity / host cell perinuclear region of cytoplasm / host cell endoplasmic reticulum membrane / protein dimerization activity / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / RNA helicase / induction by virus of host autophagy / RNA-directed RNA polymerase / viral RNA genome replication / serine-type endopeptidase activity / RNA-dependent RNA polymerase activity / virus-mediated perturbation of host defense response / fusion of virus membrane with host endosome membrane / centrosome / lipid binding / viral envelope / host cell nucleus / virion attachment to host cell / GTP binding / structural molecule activity / virion membrane / ATP hydrolysis activity / proteolysis / extracellular region / ATP binding / membrane / metal ion binding Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 22.0 Å | |||||||||
![]() | Wang JQ / Lok SM | |||||||||
![]() | ![]() Title: A Human Bi-specific Antibody against Zika Virus with High Therapeutic Potential. Authors: Jiaqi Wang / Marco Bardelli / Diego A Espinosa / Mattia Pedotti / Thiam-Seng Ng / Siro Bianchi / Luca Simonelli / Elisa X Y Lim / Mathilde Foglierini / Fabrizia Zatta / Stefano Jaconi / ...Authors: Jiaqi Wang / Marco Bardelli / Diego A Espinosa / Mattia Pedotti / Thiam-Seng Ng / Siro Bianchi / Luca Simonelli / Elisa X Y Lim / Mathilde Foglierini / Fabrizia Zatta / Stefano Jaconi / Martina Beltramello / Elisabetta Cameroni / Guntur Fibriansah / Jian Shi / Taylor Barca / Isabel Pagani / Alicia Rubio / Vania Broccoli / Elisa Vicenzi / Victoria Graham / Steven Pullan / Stuart Dowall / Roger Hewson / Simon Jurt / Oliver Zerbe / Karin Stettler / Antonio Lanzavecchia / Federica Sallusto / Andrea Cavalli / Eva Harris / Shee-Mei Lok / Luca Varani / Davide Corti / ![]() ![]() ![]() ![]() ![]() Abstract: Zika virus (ZIKV), a mosquito-borne flavivirus, causes devastating congenital birth defects. We isolated a human monoclonal antibody (mAb), ZKA190, that potently cross-neutralizes multi-lineage ZIKV ...Zika virus (ZIKV), a mosquito-borne flavivirus, causes devastating congenital birth defects. We isolated a human monoclonal antibody (mAb), ZKA190, that potently cross-neutralizes multi-lineage ZIKV strains. ZKA190 is highly effective in vivo in preventing morbidity and mortality of ZIKV-infected mice. NMR and cryo-electron microscopy show its binding to an exposed epitope on DIII of the E protein. ZKA190 Fab binds all 180 E protein copies, altering the virus quaternary arrangement and surface curvature. However, ZIKV escape mutants emerged in vitro and in vivo in the presence of ZKA190, as well as of other neutralizing mAbs. To counter this problem, we developed a bispecific antibody (FIT-1) comprising ZKA190 and a second mAb specific for DII of E protein. In addition to retaining high in vitro and in vivo potencies, FIT-1 robustly prevented viral escape, warranting its development as a ZIKV immunotherapy. #1: ![]() Title: Cryo-EM structure of zika virus complexed with a human monoclonal antibody Authors: Wang JQ / Lok SM | |||||||||
History |
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Structure visualization
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 27.2 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 16.1 KB 16.1 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 6.8 KB | Display | ![]() |
Images | ![]() | 166.2 KB | ||
Filedesc metadata | ![]() | 6 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 5y0aMC ![]() 6794C ![]() 5omzC M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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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 | Zika virus complexed with the Fab molecule of a human monoclonal antibody named ZKA190 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 3.42 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
-Entire : zika virus complexed with Fab of a human monoclonal antibody name...
Entire | Name: zika virus complexed with Fab of a human monoclonal antibody named ZKA190 |
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Components |
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-Supramolecule #1: zika virus complexed with Fab of a human monoclonal antibody name...
Supramolecule | Name: zika virus complexed with Fab of a human monoclonal antibody named ZKA190 type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: ![]() ![]() |
-Supramolecule #2: zika virus
Supramolecule | Name: zika virus / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #2 |
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-Supramolecule #3: Fab ZKA190
Supramolecule | Name: Fab ZKA190 / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #3 |
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-Macromolecule #1: protein E
Macromolecule | Name: protein E / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 44.06993 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: IRCIGVSNRD FVEGMSGGTW VDVVLEHGGC VTVMAQDKPT VDIELVTTTV SNMAEVRSYC YEASISDMAS DSRCPTQGEA YLDKQSDTQ YVCKRTLVDR GWGNGCGLFG KGSLVTCAKF ACSKKMTGKS IQPENLEYRI MLSVHGSQHS GMIVNDTGHE T DENRAKVE ...String: IRCIGVSNRD FVEGMSGGTW VDVVLEHGGC VTVMAQDKPT VDIELVTTTV SNMAEVRSYC YEASISDMAS DSRCPTQGEA YLDKQSDTQ YVCKRTLVDR GWGNGCGLFG KGSLVTCAKF ACSKKMTGKS IQPENLEYRI MLSVHGSQHS GMIVNDTGHE T DENRAKVE ITPNSPRAEA TLGGFGSLGL DCEPRTGLDF SDLYYLTMNN KHWLVHKEWF HDIPLPWHAG ADTGTPHWNN KE ALVEFKD AHAKRQTVVV LGSQEGAVHT ALAGALEAEM DGAKGRLSSG HLKCRLKMDK LRLKGVSYSL CTAAFTFTKI PAE TLHGTV TVEVQYAGTD GPCKVPAQMA VDMQTLTPVG RLITANPVIT ESTENSKMML ELDPPFGDSY IVIGVGEKKI THHW HRS UniProtKB: Core protein |
-Macromolecule #2: variable region of Fab ZKA190 heavy chain
Macromolecule | Name: variable region of Fab ZKA190 heavy chain / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 14.41001 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: QVQLVESGGG VVQPGRSLRL SCAASGFTFS KYGMHWVRQA PGKGLEWVAV ISYEGSNKYY ADSVKGRFTI SRDNSKNTLY LQMNSLRAE DTAVYYCAKS GTQYYDTTGY EYRGLEYFGY WGQGTLVTVS |
-Macromolecule #3: variable region of Fab ZKA190 light chain
Macromolecule | Name: variable region of Fab ZKA190 light chain / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 11.935241 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: EIVLTQSPGT LSLSPGERAT LSCRASQSVS SSYLAWYQQK RGQAPRLLIY DASSRATGIP DRFSGSGSGT DFTLTISRLE PEDFAVYYC QQYGRSRWTF GQGTKVEIK |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 1 mg/mL | ||||||||
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Buffer | pH: 8 Component:
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Grid | Material: COPPER / Support film - Material: CARBON / Support film - topology: LACEY / Pretreatment - Type: GLOW DISCHARGE | ||||||||
Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: FEI FALCON II (4k x 4k) / Average electron dose: 20.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
-Atomic model buiding 1
Refinement | Protocol: RIGID BODY FIT |
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Output model | ![]() PDB-5y0a: |