[English] 日本語
Yorodumi- EMDB-9575: Cryo-EM structure of zika virus complexed with Fab C10 at pH 8.0 -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-9575 | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Title | Cryo-EM structure of zika virus complexed with Fab C10 at pH 8.0 | ||||||||||||
Map data | |||||||||||||
Sample |
| ||||||||||||
Function / homology | Function and homology information 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 / protein dimerization activity / host cell endoplasmic reticulum membrane / 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 / GTP binding / virion attachment to host cell / virion membrane / structural molecule activity / ATP hydrolysis activity / proteolysis / extracellular region / ATP binding / membrane / metal ion binding Similarity search - Function | ||||||||||||
Biological species | Zika virus / ZIKV (virus) / Homo sapiens (human) | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.0 Å | ||||||||||||
Authors | Zhang S / Kostyuchenko V / Ng T-S / Lim X-N / Ooi JSG / Lambert S / Tan TY / Widman D / Shi J / Baric RS / Lok S-M | ||||||||||||
Funding support | Singapore, United States, 3 items
| ||||||||||||
Citation | Journal: Nat Commun / Year: 2016 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 |
|
-Structure visualization
Movie |
Movie viewer |
---|---|
Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_9575.map.gz | 668.1 MB | EMDB map data format | |
---|---|---|---|---|
Header (meta data) | emd-9575-v30.xml emd-9575.xml | 14.8 KB 14.8 KB | Display Display | EMDB header |
Images | emd_9575.png | 310.1 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-9575 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-9575 | HTTPS FTP |
-Validation report
Summary document | emd_9575_validation.pdf.gz | 655.2 KB | Display | EMDB validaton report |
---|---|---|---|---|
Full document | emd_9575_full_validation.pdf.gz | 654.8 KB | Display | |
Data in XML | emd_9575_validation.xml.gz | 8.5 KB | Display | |
Data in CIF | emd_9575_validation.cif.gz | 9.8 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-9575 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-9575 | HTTPS FTP |
-Related structure data
Related structure data | 5h37MC 9573C 9574C 5h30C 5h32C M: atomic model generated by this map C: citing same article (ref.) |
---|---|
Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
---|---|
Related items in Molecule of the Month |
-Map
File | Download / File: emd_9575.map.gz / Format: CCP4 / Size: 729 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.1 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
|
-Supplemental data
-Sample components
-Entire : zika virus complexed with C10 Fab at pH 8.0
Entire | Name: zika virus complexed with C10 Fab at pH 8.0 |
---|---|
Components |
|
-Supramolecule #1: zika virus complexed with C10 Fab at pH 8.0
Supramolecule | Name: zika virus complexed with C10 Fab at pH 8.0 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
---|
-Supramolecule #2: zika virus
Supramolecule | Name: zika virus / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1-#2 |
---|---|
Source (natural) | Organism: Zika virus |
-Supramolecule #3: C10 Fab
Supramolecule | Name: C10 Fab / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #3-#4 |
---|---|
Recombinant expression | Organism: Homo sapiens (human) / Recombinant cell: HEK293T / Recombinant plasmid: unknown |
-Macromolecule #1: structural protein E
Macromolecule | Name: structural protein E / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: ZIKV (virus) / Strain: Mr 766 |
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: strutural protein M
Macromolecule | Name: strutural protein M / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: ZIKV (virus) / Strain: Mr 766 |
Molecular weight | Theoretical: 8.496883 KDa |
Sequence | String: AVTLPSHSTR KLQTRSQTWL ESREYTKHLI RVENWIFRNP GFALAAAAIA WLLGSSTSQK VIYLVMILLI APAYS |
-Macromolecule #3: C10 IgG heavy chain variable region
Macromolecule | Name: C10 IgG heavy chain variable region / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 14.487058 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: EVQLVESGAE VKKPGASVKV SCKASGYTFT SYAMHWVRQA PGQRLEWMGW INAGNGNTKY SQKFQDRVTI TRDTSASTAY MELSSLRSE DTAIYYCARD KVDDYGDYWF PTLWYFDYWG QGTLVTVS |
-Macromolecule #4: C10 IgG light chain variable region
Macromolecule | Name: C10 IgG light chain variable region / type: protein_or_peptide / ID: 4 / Number of copies: 3 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 11.298362 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: SALTQPASVS GSPGQSITIS CTGTSSDVGG FNYVSWFQQH PGKAPKLMLY DVTSRPSGVS SRFSGSKSGN TASLTISGLQ AEDEADYYC SSHTSRGTWV FGGGTKLTVL |
-Macromolecule #5: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 5 / Number of copies: 1 / Formula: NAG |
---|---|
Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ChemComp-NAG: |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 8 |
---|---|
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
---|---|
Image recording | Film or detector model: FEI FALCON II (4k x 4k) / Average electron dose: 38.0 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: 4.0 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 49100 |
---|---|
Initial angle assignment | Type: COMMON LINE |
Final angle assignment | Type: COMMON LINE |