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- EMDB-25606: Zika Virus particle bound with IgM antibody DH1017 Fab fragment -
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Open data
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Basic information
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Title | Zika Virus particle bound with IgM antibody DH1017 Fab fragment | |||||||||
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![]() | Zika Virus particle / IgM / Fab fragment / Neutralization / VIRUS | |||||||||
Function / homology | ![]() positive regulation of B cell activation / phagocytosis, recognition / phagocytosis, engulfment / immunoglobulin complex, circulating / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT2 activity / immunoglobulin receptor binding / ribonucleoside triphosphate phosphatase activity / complement activation, classical pathway / antigen binding / B cell receptor signaling pathway ...positive regulation of B cell activation / phagocytosis, recognition / phagocytosis, engulfment / immunoglobulin complex, circulating / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT2 activity / immunoglobulin receptor binding / ribonucleoside triphosphate phosphatase activity / complement activation, classical pathway / antigen binding / B cell receptor signaling pathway / viral capsid / double-stranded RNA binding / antibacterial humoral response / mRNA (nucleoside-2'-O-)-methyltransferase activity / mRNA 5'-cap (guanine-N7-)-methyltransferase activity / membrane => GO:0016020 / blood microparticle / RNA helicase activity / host cell endoplasmic reticulum membrane / protein dimerization activity / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / defense response to bacterium / symbiont entry into host cell / external side of plasma membrane / viral RNA genome replication / serine-type endopeptidase activity / RNA-dependent RNA polymerase activity / innate immune response / fusion of virus membrane with host endosome membrane / host cell nucleus / virion attachment to host cell / structural molecule activity / virion membrane / proteolysis / extracellular exosome / extracellular region / ATP binding / metal ion binding / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 5.26 Å | |||||||||
![]() | Miller AS / Kuhn RJ | |||||||||
Funding support | ![]()
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![]() | ![]() Title: A Zika virus-specific IgM elicited in pregnancy exhibits ultrapotent neutralization. Authors: Tulika Singh / Kwan-Ki Hwang / Andrew S Miller / Rebecca L Jones / Cesar A Lopez / Sarah J Dulson / Camila Giuberti / Morgan A Gladden / Itzayana Miller / Helen S Webster / Joshua A Eudailey ...Authors: Tulika Singh / Kwan-Ki Hwang / Andrew S Miller / Rebecca L Jones / Cesar A Lopez / Sarah J Dulson / Camila Giuberti / Morgan A Gladden / Itzayana Miller / Helen S Webster / Joshua A Eudailey / Kan Luo / Tarra Von Holle / Robert J Edwards / Sarah Valencia / Katherine E Burgomaster / Summer Zhang / Jesse F Mangold / Joshua J Tu / Maria Dennis / S Munir Alam / Lakshmanane Premkumar / Reynaldo Dietze / Theodore C Pierson / Eng Eong Ooi / Helen M Lazear / Richard J Kuhn / Sallie R Permar / Mattia Bonsignori / ![]() ![]() ![]() ![]() Abstract: Congenital Zika virus (ZIKV) infection results in neurodevelopmental deficits in up to 14% of infants born to ZIKV-infected mothers. Neutralizing antibodies are a critical component of protective ...Congenital Zika virus (ZIKV) infection results in neurodevelopmental deficits in up to 14% of infants born to ZIKV-infected mothers. Neutralizing antibodies are a critical component of protective immunity. Here, we demonstrate that plasma IgM contributes to ZIKV immunity in pregnancy, mediating neutralization up to 3 months post-symptoms. From a ZIKV-infected pregnant woman, we isolated a pentameric ZIKV-specific IgM (DH1017.IgM) that exhibited ultrapotent ZIKV neutralization dependent on the IgM isotype. DH1017.IgM targets an envelope dimer epitope within domain II. The epitope arrangement on the virion is compatible with concurrent engagement of all ten antigen-binding sites of DH1017.IgM, a solution not available to IgG. DH1017.IgM protected mice against viremia upon lethal ZIKV challenge more efficiently than when expressed as an IgG. Our findings identify a role for antibodies of the IgM isotype in protection against ZIKV and posit DH1017.IgM as a safe and effective candidate immunotherapeutic, particularly during pregnancy. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 66.1 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 18.4 KB 18.4 KB | Display Display | ![]() |
Images | ![]() | 238.3 KB | ||
Filedesc metadata | ![]() | 6.1 KB | ||
Others | ![]() ![]() | 521.8 MB 521.7 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7t17MC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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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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Voxel size | X=Y=Z: 2.6 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #1
File | emd_25606_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_25606_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
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Sample components
-Entire : Zika virus
Entire | Name: ![]() ![]() |
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Components |
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-Supramolecule #1: Zika virus
Supramolecule | Name: Zika virus / type: virus / ID: 1 / Parent: 0 / Macromolecule list: all / NCBI-ID: 64320 / Sci species name: Zika virus / Virus type: VIRION / Virus isolate: STRAIN / Virus enveloped: Yes / Virus empty: No |
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-Macromolecule #1: DH1017.IgM FabC constant domain
Macromolecule | Name: DH1017.IgM FabC constant domain / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 10.830188 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: ASTKGPSVFP LAPSSKSTSG GTAALGCLVK DYFPEPVTVS WNSGALTSGV HTFPAVLQSS GLYSLSSVVT VPSSSLGTQT YICNVNHKP SNTKVDKKVE PKSCDK UniProtKB: Immunoglobulin gamma-1 heavy chain |
-Macromolecule #2: DH1017.IgM LambdaC constant domain
Macromolecule | Name: DH1017.IgM LambdaC constant domain / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 11.36157 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: GQPKANPTVT LFPPSSEELQ ANKATLVCLI SDFYPGAVTV AWKADSSPVK AGVETTTPSK QSNNKYAASS YLSLTPEQWK SHRSYSCQV THEGSTVEKT VAPTECS UniProtKB: Immunoglobulin lambda-like polypeptide 5 |
-Macromolecule #3: DH1017.IgM IgH
Macromolecule | Name: DH1017.IgM IgH / type: protein_or_peptide / ID: 3 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 13.325816 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: QVQLQESGPG LVKPSQTLSL TCAVSGGSIS SGDSYWSWIR QHPGKGLEWI GSIYYSGSTY YNPSLKSRVT IPIDTSKNQF SLKLSSVTA ADTAVYYCAR HVGDLRVNDA FDIWGQGTMV TVSS |
-Macromolecule #4: DH1017.IgM IgL
Macromolecule | Name: DH1017.IgM IgL / type: protein_or_peptide / ID: 4 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 11.48275 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: QSVLTQPPSV SAAPGQKVTI SCSGSSSNIG NNFVSWYQRL PGTPPKLLIY DSDKRPSGIP DRFSGSKSGT SATLGITGLQ TGDEGDYYC GTWDRSLSVV VFGGGTKLTV L |
-Macromolecule #5: Core protein
Macromolecule | Name: Core protein / type: protein_or_peptide / ID: 5 / Number of copies: 3 / Enantiomer: LEVO / EC number: flavivirin |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 42.623277 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 IVIGVG UniProtKB: Genome polyprotein |
-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: 8 |
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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: GATAN K3 (6k x 4k) / Average electron dose: 35.0 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: OTHER |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 5.26 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 4104 |
Initial angle assignment | Type: RANDOM ASSIGNMENT |
Final angle assignment | Type: PROJECTION MATCHING |