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- EMDB-9574: Cryo-EM structure of zika virus complexed with Fab C10 at pH 5.0 -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-9574 | ||||||||||||
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Title | Cryo-EM structure of zika virus complexed with Fab C10 at pH 5.0 | ||||||||||||
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![]() | Antibody / VIRUS-IMMUNE SYSTEM complex | ||||||||||||
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 / viral capsid / double-stranded RNA binding / nucleoside-triphosphate phosphatase / 4 iron, 4 sulfur cluster binding / mRNA (guanine-N7)-methyltransferase ...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 / 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 / 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: 12.0 Å | ||||||||||||
![]() | Zhang S / Kostyuchenko V | ||||||||||||
Funding support | ![]() ![]()
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![]() | ![]() Title: Neutralization mechanism of a highly potent antibody against Zika virus. Authors: Shuijun Zhang / Victor A Kostyuchenko / Thiam-Seng Ng / Xin-Ni Lim / Justin S G Ooi / Sebastian Lambert / Ter Yong Tan / Douglas G Widman / Jian Shi / Ralph S Baric / Shee-Mei Lok / ![]() ![]() Abstract: The rapid spread of Zika virus (ZIKV), which causes microcephaly and Guillain-Barré syndrome, signals an urgency to identify therapeutics. Recent efforts to rescreen dengue virus human antibodies ...The rapid spread of Zika virus (ZIKV), which causes microcephaly and Guillain-Barré syndrome, signals an urgency to identify therapeutics. Recent efforts to rescreen dengue virus human antibodies for ZIKV cross-neutralization activity showed antibody C10 as one of the most potent. To investigate the ability of the antibody to block fusion, we determined the cryoEM structures of the C10-ZIKV complex at pH levels mimicking the extracellular (pH8.0), early (pH6.5) and late endosomal (pH5.0) environments. The 4.0 Å resolution pH8.0 complex structure shows that the antibody binds to E proteins residues at the intra-dimer interface, and the virus quaternary structure-dependent inter-dimer and inter-raft interfaces. At pH6.5, antibody C10 locks all virus surface E proteins, and at pH5.0, it locks the E protein raft structure, suggesting that it prevents the structural rearrangement of the E proteins during the fusion event-a vital step for infection. This suggests antibody C10 could be a good therapeutic candidate. | ||||||||||||
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 | ![]() | 48.6 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 12.4 KB 12.4 KB | Display Display | ![]() |
Images | ![]() | 209.7 KB | ||
Filedesc metadata | ![]() | 5.6 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 5h32MC ![]() 9573C ![]() 9575C ![]() 5h30C ![]() 5h37C 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
File | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Voxel size | X=Y=Z: 3.44 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 C10 at pH 5.0
Entire | Name: zika virus complexed with Fab C10 at pH 5.0 |
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Components |
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-Supramolecule #1: zika virus complexed with Fab C10 at pH 5.0
Supramolecule | Name: zika virus complexed with Fab C10 at pH 5.0 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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-Supramolecule #2: zika virus
Supramolecule | Name: zika virus / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() ![]() |
-Supramolecule #3: Fab C10
Supramolecule | Name: Fab C10 / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2-#3 |
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-Macromolecule #1: structural protein E
Macromolecule | Name: structural 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 |
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: Genome polyprotein |
-Macromolecule #2: C10 IgG heavy chain variable region
Macromolecule | Name: C10 IgG heavy chain variable region / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 14.487058 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: EVQLVESGAE VKKPGASVKV SCKASGYTFT SYAMHWVRQA PGQRLEWMGW INAGNGNTKY SQKFQDRVTI TRDTSASTAY MELSSLRSE DTAIYYCARD KVDDYGDYWF PTLWYFDYWG QGTLVTVS |
-Macromolecule #3: C10 IgG light chain variable region
Macromolecule | Name: C10 IgG light chain variable region / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 11.298362 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: SALTQPASVS GSPGQSITIS CTGTSSDVGG FNYVSWFQQH PGKAPKLMLY DVTSRPSGVS SRFSGSKSGN TASLTISGLQ AEDEADYYC SSHTSRGTWV FGGGTKLTVL |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 5 |
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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 |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Startup model | Type of model: EMDB MAP |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 12.0 Å / Resolution method: FSC 0.5 CUT-OFF / Number images used: 23810 |
Initial angle assignment | Type: COMMON LINE |
Final angle assignment | Type: COMMON LINE |