+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-30337 | |||||||||
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Title | CryoEM structure of Zika virus with Fab at 4.1 Angstrom | |||||||||
Map data | ||||||||||
Sample |
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Function / homology | Function and homology information flavivirin / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of host TYK2 activity / 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 / viral capsid / double-stranded RNA binding / nucleoside-triphosphate phosphatase / 4 iron, 4 sulfur cluster binding / mRNA (guanine-N7)-methyltransferase ...flavivirin / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of host TYK2 activity / 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 / 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 / mRNA (nucleoside-2'-O-)-methyltransferase activity / mRNA 5'-cap (guanine-N7-)-methyltransferase activity / molecular adaptor activity / RNA helicase activity / host cell perinuclear region of cytoplasm / protein dimerization activity / host cell endoplasmic reticulum membrane / RNA helicase / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / 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 | Zika virus / Homo sapiens (human) / ZIKV (virus) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.1 Å | |||||||||
Authors | Tyagi A / Ahmed T / Shi J / Bhushan S | |||||||||
Funding support | 1 items
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Citation | Journal: J Struct Biol X / Year: 2020 Title: A complex between the Zika virion and the Fab of a broadly cross-reactive neutralizing monoclonal antibody revealed by cryo-EM and single particle analysis at 4.1 Å resolution. Authors: Anu Tyagi / Tofayel Ahmed / Jian Shi / Shashi Bhushan / Abstract: Zika virus (ZIKV) recently emerged as a major public health concern because it can cause fetal microcephaly and neurological disease such as the Guillain-Barré syndrome. A particularly potent class ...Zika virus (ZIKV) recently emerged as a major public health concern because it can cause fetal microcephaly and neurological disease such as the Guillain-Barré syndrome. A particularly potent class of broadly neutralizing antibodies (nAbs) targets a quaternary epitope located at the interface of two envelope proteins monomers, exposed at the surface of the mature virion. This "E-dimer-dependent epitope" (EDE), comprises the fusion loop of one monomer at the tip of domain II of E and a portion of the domains I and III of the adjacent monomer. Since this epitope largely overlaps with the binding site of the precursor membrane protein (prM) during Zika virion maturation, its molecular surface is evolutionary conserved in flaviviruses such as Dengue and Zika viruses, and can elicit antibodies that broadly neutralize various ZIKV strains. Here, we present a cryo-EM reconstruction at 4.1 Å resolution of the virion bound to the antigen binding fragment (Fab) of an antibody that targets this mutationally-constrained quaternary epitope. The Fab incompletely covers the surface of the virion as it does not bind next to its 5-fold icosahedral axes. The structure reveals details of the binding mode of this potent neutralizing class of antibodies and can inform the design of immunogens and vaccines targeting this conserved epitope. | |||||||||
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_30337.map.gz | 166.7 MB | EMDB map data format | |
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Header (meta data) | emd-30337-v30.xml emd-30337.xml | 13.1 KB 13.1 KB | Display Display | EMDB header |
Images | emd_30337.png | 119.7 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-30337 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-30337 | HTTPS FTP |
-Validation report
Summary document | emd_30337_validation.pdf.gz | 360.5 KB | Display | EMDB validaton report |
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Full document | emd_30337_full_validation.pdf.gz | 360 KB | Display | |
Data in XML | emd_30337_validation.xml.gz | 10 KB | Display | |
Data in CIF | emd_30337_validation.cif.gz | 11.6 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-30337 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-30337 | HTTPS FTP |
-Related structure data
Related structure data | 7cbpMC 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_30337.map.gz / Format: CCP4 / Size: 1.9 GB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.045 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 : Zika virus
Entire | Name: Zika virus |
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Components |
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-Supramolecule #1: Zika virus
Supramolecule | Name: Zika virus / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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-Supramolecule #2: Zika virus M and E proteins
Supramolecule | Name: Zika virus M and E proteins / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: Zika virus |
-Supramolecule #3: FAB
Supramolecule | Name: FAB / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #3-#4 |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Small envelope protein M
Macromolecule | Name: Small envelope protein M / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ZIKV (virus) |
Molecular weight | Theoretical: 8.496883 KDa |
Sequence | String: AVTLPSHSTR KLQTRSQTWL ESREYTKHLI RVENWIFRNP GFALAAAAIA WLLGSSTSQK VIYLVMILLI APAYS |
-Macromolecule #2: Envelope protein E
Macromolecule | Name: Envelope protein E / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ZIKV (virus) |
Molecular weight | Theoretical: 54.186762 KDa |
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 HRSGS TIGKAFEATV RGAKRMAVLG DTAWDFGSVG GALNSLGKGI HQIFGAAFKS LFGGMSWFSQ ILIGTLLMWL GLNTK NGSI SLMCLALGGV LIFLSTA |
-Macromolecule #3: Fab Heavy chain
Macromolecule | Name: Fab Heavy chain / type: protein_or_peptide / ID: 3 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 23.612326 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: EVQLLESGGG LVQPGGSLRL SCAASGFSFS TYSMHWVRQA PGKGLEWVSA ISGEGDSAYY ADSVKGRFTI SRDNSKNTLY LQMNKVRAE DTAVYYCVGG YSNFYYYYTM DAWGQGTMVT VSSASTKGPS VFPLAPSSKS TSGGTAALGC LVKDYFPEPV T VSWNSGAL ...String: EVQLLESGGG LVQPGGSLRL SCAASGFSFS TYSMHWVRQA PGKGLEWVSA ISGEGDSAYY ADSVKGRFTI SRDNSKNTLY LQMNKVRAE DTAVYYCVGG YSNFYYYYTM DAWGQGTMVT VSSASTKGPS VFPLAPSSKS TSGGTAALGC LVKDYFPEPV T VSWNSGAL TSGVHTFPAV LQSSGLYSLS SVVTVPSSSL GTQTYICNVN HKPSNTKVDK KVEP |
-Macromolecule #4: Fab light chain
Macromolecule | Name: Fab light chain / type: protein_or_peptide / ID: 4 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 23.818539 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: DIVMTQSPAS LSLSPGERAT LSCRATQSIS TFLAWYQQKP GQAPRLLIYD ASTRASGIPA RFSGSRSGTD FTLTITRLEP EDFAVYYCQ QRYNWPPYSF GQGTKLEIKR TVAAPSVFIF PPSDEQLKSG TASVVCLLNN FYPREAKVQW KVDNALQSGN S QESVTEQD ...String: DIVMTQSPAS LSLSPGERAT LSCRATQSIS TFLAWYQQKP GQAPRLLIYD ASTRASGIPA RFSGSRSGTD FTLTITRLEP EDFAVYYCQ QRYNWPPYSF GQGTKLEIKR TVAAPSVFIF PPSDEQLKSG TASVVCLLNN FYPREAKVQW KVDNALQSGN S QESVTEQD SKDSTYSLSS TLTLSKADYE KHKVYACEVT HQGLSSPVTK SFNRGEC |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 8 |
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Vitrification | Cryogen name: ETHANE |
-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: 48.0 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 |
-Image processing
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 4.1 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 4610 |
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Initial angle assignment | Type: OTHER |
Final angle assignment | Type: OTHER |