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- EMDB-9131: Cryo-EM structure of the ZIKV virion in complex with Fab fragment... -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-9131 | |||||||||
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Title | Cryo-EM structure of the ZIKV virion in complex with Fab fragments of the potently neutralizing human monoclonal antibody ZIKV-195 | |||||||||
![]() | ZIKV virion in complex with Fab fragments of the potently neutralizing human monoclonal antibody ZIKV-195. Different contour levels are required to visualize the viral components and the bound Fab molecules. | |||||||||
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Function / homology | ![]() immunoglobulin complex / 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 / viral capsid / double-stranded RNA binding / nucleoside-triphosphate phosphatase / 4 iron, 4 sulfur cluster binding ...immunoglobulin complex / 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 / 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 / adaptive immune response / mRNA 5'-cap (guanine-N7-)-methyltransferase activity / 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 / immune response / 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 space / extracellular region / ATP binding / membrane / metal ion binding / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.0 Å | |||||||||
![]() | Long F / Rossmann MG | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural basis of a potent human monoclonal antibody against Zika virus targeting a quaternary epitope. Authors: Feng Long / Michael Doyle / Estefania Fernandez / Andrew S Miller / Thomas Klose / Madhumati Sevvana / Aubrey Bryan / Edgar Davidson / Benjamin J Doranz / Richard J Kuhn / Michael S Diamond ...Authors: Feng Long / Michael Doyle / Estefania Fernandez / Andrew S Miller / Thomas Klose / Madhumati Sevvana / Aubrey Bryan / Edgar Davidson / Benjamin J Doranz / Richard J Kuhn / Michael S Diamond / James E Crowe / Michael G Rossmann / ![]() Abstract: Zika virus (ZIKV) is a major human pathogen and member of the genus in the Flaviviridae family. In contrast to most other insect-transmitted flaviviruses, ZIKV also can be transmitted sexually and ...Zika virus (ZIKV) is a major human pathogen and member of the genus in the Flaviviridae family. In contrast to most other insect-transmitted flaviviruses, ZIKV also can be transmitted sexually and from mother to fetus in humans. During recent outbreaks, ZIKV infections have been linked to microcephaly, congenital disease, and Guillain-Barré syndrome. Neutralizing antibodies have potential as therapeutic agents. We report here a 4-Å-resolution cryo-electron microscopy structure of the ZIKV virion in complex with Fab fragments of the potently neutralizing human monoclonal antibody ZIKV-195. The footprint of the ZIKV-195 Fab fragment expands across two adjacent envelope (E) protein protomers. ZIKV neutralization by this antibody is presumably accomplished by cross-linking the E proteins, which likely prevents formation of E protein trimers required for fusion of the viral and cellular membranes. A single dose of ZIKV-195 administered 5 days after virus inoculation showed marked protection against lethality in a stringent mouse model of infection. | |||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 478.8 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 21.8 KB 21.8 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() ![]() | 21 KB 21 KB | Display Display | ![]() |
Images | ![]() | 287.6 KB | ||
Others | ![]() ![]() | 130.1 MB 130.1 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6midMC 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 | ZIKV virion in complex with Fab fragments of the potently neutralizing human monoclonal antibody ZIKV-195. Different contour levels are required to visualize the viral components and the bound Fab molecules. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.62 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Half map: Half map #1
File | emd_9131_half_map_1.map | ||||||||||||
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Annotation | Half map #1 | ||||||||||||
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Density Histograms |
-Half map: Half map #2
File | emd_9131_half_map_2.map | ||||||||||||
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Annotation | Half map #2 | ||||||||||||
Projections & Slices |
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Density Histograms |
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Sample components
-Entire : ZIKV virion in complex with Fab fragments of the potently neutral...
Entire | Name: ZIKV virion in complex with Fab fragments of the potently neutralizing human monoclonal antibody ZIKV-195 |
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Components |
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-Supramolecule #1: ZIKV virion in complex with Fab fragments of the potently neutral...
Supramolecule | Name: ZIKV virion in complex with Fab fragments of the potently neutralizing human monoclonal antibody ZIKV-195 type: complex / ID: 1 / Parent: 0 / Macromolecule list: all Details: Purified from infected Vero cells overexpressing the furin protease |
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-Supramolecule #3: monoclonal antibody ZIKV-195
Supramolecule | Name: monoclonal antibody ZIKV-195 / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #3-#4 |
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Source (natural) | Organism: ![]() |
-Supramolecule #2: Zika virus (isolate ZIKV/Human/French Polynesia/10087PF/2013)
Supramolecule | Name: Zika virus (isolate ZIKV/Human/French Polynesia/10087PF/2013) type: virus / ID: 2 / Parent: 1 / Macromolecule list: #1-#2 / NCBI-ID: 2043570 Sci species name: Zika virus (isolate ZIKV/Human/French Polynesia/10087PF/2013) Sci species strain: isolate ZIKV/Human/French Polynesia/10087PF/2013 Virus type: VIRION / Virus isolate: STRAIN / Virus enveloped: Yes / Virus empty: No |
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-Macromolecule #1: E protein
Macromolecule | Name: E protein / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 54.444051 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 LIFLSTAVSA |
-Macromolecule #2: M protein
Macromolecule | Name: M protein / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 8.496883 KDa |
Sequence | String: AVTLPSHSTR KLQTRSQTWL ESREYTKHLI RVENWIFRNP GFALAAAAIA WLLGSSTSQK VIYLVMILLI APAYS |
-Macromolecule #3: monoclonal antibody ZIKV-195 heavy chain
Macromolecule | Name: monoclonal antibody ZIKV-195 heavy chain / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 14.148739 KDa |
Sequence | String: QVQLVESGGG VVHPGRSLRL SCAASGFTFS SSAMHWVRQA PGKGLEWVAV ISYDGSNKYY GDSVKGRFTI SRDNSKNTLY LQMHSLRAE DTAVYYCAKD RDAYNTVGYF AYYYGMDVWG QGTLVTVSS |
-Macromolecule #4: monoclonal antibody ZIKV-195 light chain
Macromolecule | Name: monoclonal antibody ZIKV-195 light chain / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 11.750902 KDa |
Sequence | String: QSVLTQPPSV SEAPRQRVTI SCSGSSSNIG NNAVNWYQQL PGKAPKLLIY YDDLLPSGVS DRFSGSKSGT SASLAISGLQ SEDEADYYC AAWDDSLTRY VFGTGTKVTV L |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 1.00 mg/mL | ||||||||||||
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Buffer | pH: 8 Component:
Details: NTE buffer at pH 8.0 | ||||||||||||
Grid | Details: unspecified | ||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 90 % / Chamber temperature: 298 K / Instrument: GATAN CRYOPLUNGE 3 | ||||||||||||
Details | Fab fragments were mixed with purified mature virus particles to make complexes. |
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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 / Number real images: 1691 / Average electron dose: 30.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
-Atomic model buiding 1
Initial model | PDB ID: |
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Details | The occupancy of bound Fabs was low. Due to poor density, only the variable domain of Fab molecule was modeled and fit into one of the three Fab binding sites on each icosahedral asymmetric unit. |
Refinement | Space: REAL / Protocol: FLEXIBLE FIT |
Output model | ![]() PDB-6mid: |