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- EMDB-25606: Zika Virus particle bound with IgM antibody DH1017 Fab fragment -

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Basic information

Entry
Database: EMDB / ID: EMD-25606
TitleZika Virus particle bound with IgM antibody DH1017 Fab fragment
Map data
Sample
  • Virus: Zika virus
    • Protein or peptide: DH1017.IgM FabC constant domain
    • Protein or peptide: DH1017.IgM LambdaC constant domain
    • Protein or peptide: DH1017.IgM IgH
    • Protein or peptide: DH1017.IgM IgL
    • Protein or peptide: Core proteinCapsid
Function / homology
Function and homology information


positive regulation of B cell activation / phagocytosis, recognition / phagocytosis, engulfment / immunoglobulin complex, circulating / immunoglobulin receptor binding / immunoglobulin complex / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT2 activity / complement activation, classical pathway / antigen binding / ribonucleoside triphosphate phosphatase activity ...positive regulation of B cell activation / phagocytosis, recognition / phagocytosis, engulfment / immunoglobulin complex, circulating / immunoglobulin receptor binding / immunoglobulin complex / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT2 activity / complement activation, classical pathway / antigen binding / ribonucleoside triphosphate phosphatase activity / B cell receptor signaling pathway / viral capsid / double-stranded RNA binding / mRNA (nucleoside-2'-O-)-methyltransferase activity / mRNA 5'-cap (guanine-N7-)-methyltransferase activity / RNA helicase activity / adaptive immune response / membrane => GO:0016020 / host cell endoplasmic reticulum membrane / protein dimerization activity / defense response to bacterium / symbiont entry into host cell / viral RNA genome replication / external side of plasma membrane / RNA-dependent RNA polymerase activity / serine-type endopeptidase activity / innate immune response / fusion of virus membrane with host endosome membrane / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / host cell nucleus / structural molecule activity / virion attachment to host cell / virion membrane / proteolysis / extracellular exosome / extracellular region / ATP binding / metal ion binding / plasma membrane
Similarity search - Function
Flavivirus capsid protein C superfamily / Flavivirus non-structural protein NS2B / Flavivirus non-structural protein NS4A / Flavivirus non-structural protein NS2B / Flavivirus capsid protein C / Flavivirus non-structural protein NS4B / mRNA cap 0/1 methyltransferase / Flavivirus capsid protein C / Flavivirus non-structural protein NS4B / Flavivirus non-structural protein NS4A ...Flavivirus capsid protein C superfamily / Flavivirus non-structural protein NS2B / Flavivirus non-structural protein NS4A / Flavivirus non-structural protein NS2B / Flavivirus capsid protein C / Flavivirus non-structural protein NS4B / mRNA cap 0/1 methyltransferase / Flavivirus capsid protein C / Flavivirus non-structural protein NS4B / Flavivirus non-structural protein NS4A / Flavivirus NS2B domain profile. / mRNA cap 0 and cap 1 methyltransferase (EC 2.1.1.56 and EC 2.1.1.57) domain profile. / Flavivirus non-structural protein NS2A / Flavivirus non-structural protein NS2A / Flavivirus NS3, petidase S7 / Peptidase S7, Flavivirus NS3 serine protease / Flavivirus NS3 protease (NS3pro) domain profile. / Envelope glycoprotein M, flavivirus / Flavivirus envelope glycoprotein M / RNA-directed RNA polymerase, flavivirus / Flavivirus RNA-directed RNA polymerase, fingers and palm domains / Flavivirus non-structural Protein NS1 / Flavivirus non-structural protein NS1 / Envelope glycoprotein M superfamily, flavivirus / Flavivirus polyprotein propeptide / Flavivirus polyprotein propeptide superfamily / Flavivirus polyprotein propeptide / Flaviviral glycoprotein E, central domain, subdomain 1 / Flaviviral glycoprotein E, central domain, subdomain 2 / Flavivirus envelope glycoprotein E, Stem/Anchor domain / Flavivirus glycoprotein E, immunoglobulin-like domain / Flavivirus envelope glycoprotein E, Stem/Anchor domain superfamily / Flavivirus glycoprotein, immunoglobulin-like domain / Flavivirus glycoprotein central and dimerisation domain / Flavivirus glycoprotein, central and dimerisation domains / Ribosomal RNA methyltransferase, FtsJ domain / FtsJ-like methyltransferase / Flavivirus/Alphavirus glycoprotein, immunoglobulin-like domain superfamily / Flavivirus glycoprotein, central and dimerisation domain superfamily / Flaviviral glycoprotein E, dimerisation domain / DEAD box, Flavivirus / Flavivirus DEAD domain / Immunoglobulin V-Type / Immunoglobulin V-set domain / Immunoglobulin V-set domain / helicase superfamily c-terminal domain / Immunoglobulin E-set / Superfamilies 1 and 2 helicase C-terminal domain profile. / Superfamilies 1 and 2 helicase ATP-binding type-1 domain profile. / DEAD-like helicases superfamily / Helicase, C-terminal / Helicase superfamily 1/2, ATP-binding domain / Immunoglobulin subtype / Immunoglobulin / Immunoglobulin/major histocompatibility complex, conserved site / Immunoglobulins and major histocompatibility complex proteins signature. / Immunoglobulin C-Type / Immunoglobulin C1-set / Immunoglobulin C1-set domain / RNA-directed RNA polymerase, catalytic domain / RdRp of positive ssRNA viruses catalytic domain profile. / Ig-like domain profile. / Immunoglobulin-like domain / Immunoglobulin-like domain superfamily / S-adenosyl-L-methionine-dependent methyltransferase superfamily / Peptidase S1, PA clan / DNA/RNA polymerase superfamily / Immunoglobulin-like fold / P-loop containing nucleoside triphosphate hydrolase
Similarity search - Domain/homology
Genome polyprotein / Immunoglobulin lambda-like polypeptide 5 / Immunoglobulin gamma-1 heavy chain
Similarity search - Component
Biological speciesHomo sapiens (human) / Zika virus
Methodsingle particle reconstruction / cryo EM / Resolution: 5.26 Å
AuthorsMiller AS / Kuhn RJ
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID) United States
CitationJournal: Cell / Year: 2022
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
DepositionDec 1, 2021-
Header (metadata) releaseNov 23, 2022-
Map releaseNov 23, 2022-
UpdateDec 21, 2022-
Current statusDec 21, 2022Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_25606.png

Downloads & links

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Map

FileDownload / File: emd_25606.map.gz / Format: CCP4 / Size: 512 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Voxel sizeX=Y=Z: 2.6 Å
Density
Contour LevelBy AUTHOR: 3.8
Minimum - Maximum-13.76398 - 28.140957
Average (Standard dev.)0.023048181 (±0.76627)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin-256-256-256
Dimensions512512512
Spacing512512512
CellA=B=C: 1331.2 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #1

Fileemd_25606_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #2

Fileemd_25606_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : Zika virus

EntireName: Zika virus
Components
  • Virus: Zika virus
    • Protein or peptide: DH1017.IgM FabC constant domain
    • Protein or peptide: DH1017.IgM LambdaC constant domain
    • Protein or peptide: DH1017.IgM IgH
    • Protein or peptide: DH1017.IgM IgL
    • Protein or peptide: Core proteinCapsid

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Supramolecule #1: Zika virus

SupramoleculeName: 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

MacromoleculeName: DH1017.IgM FabC constant domain / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 10.830188 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
ASTKGPSVFP LAPSSKSTSG GTAALGCLVK DYFPEPVTVS WNSGALTSGV HTFPAVLQSS GLYSLSSVVT VPSSSLGTQT YICNVNHKP SNTKVDKKVE PKSCDK

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Macromolecule #2: DH1017.IgM LambdaC constant domain

MacromoleculeName: DH1017.IgM LambdaC constant domain / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 11.36157 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
GQPKANPTVT LFPPSSEELQ ANKATLVCLI SDFYPGAVTV AWKADSSPVK AGVETTTPSK QSNNKYAASS YLSLTPEQWK SHRSYSCQV THEGSTVEKT VAPTECS

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Macromolecule #3: DH1017.IgM IgH

MacromoleculeName: DH1017.IgM IgH / type: protein_or_peptide / ID: 3 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 13.325816 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
QVQLQESGPG LVKPSQTLSL TCAVSGGSIS SGDSYWSWIR QHPGKGLEWI GSIYYSGSTY YNPSLKSRVT IPIDTSKNQF SLKLSSVTA ADTAVYYCAR HVGDLRVNDA FDIWGQGTMV TVSS

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Macromolecule #4: DH1017.IgM IgL

MacromoleculeName: DH1017.IgM IgL / type: protein_or_peptide / ID: 4 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 11.48275 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
QSVLTQPPSV SAAPGQKVTI SCSGSSSNIG NNFVSWYQRL PGTPPKLLIY DSDKRPSGIP DRFSGSKSGT SATLGITGLQ TGDEGDYYC GTWDRSLSVV VFGGGTKLTV L

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Macromolecule #5: Core protein

MacromoleculeName: Core protein / type: protein_or_peptide / ID: 5 / Number of copies: 3 / Enantiomer: LEVO / EC number: flavivirin
Source (natural)Organism: Zika virus
Molecular weightTheoretical: 42.623277 KDa
SequenceString: 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

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 8
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 35.0 e/Å2
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Initial angle assignmentType: RANDOM ASSIGNMENT
Final angle assignmentType: PROJECTION MATCHING
Final reconstructionResolution.type: BY AUTHOR / Resolution: 5.26 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 4104

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