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- EMDB-65564: DENV2 non-structural protein 1 (NS1) Stable Tetramer complexed wi... -

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Basic information

Entry
Database: EMDB / ID: EMD-65564
TitleDENV2 non-structural protein 1 (NS1) Stable Tetramer complexed with Heparin
Map dataUnsharpened map
Sample
  • Complex: DENV2 non-structural protein 1 complexed with heparin
    • Protein or peptide: Non-structural protein 1
KeywordsDengue virus / non-structural protein 1 / flavivirus / heparin / VIRAL PROTEIN
Function / homology
Function and homology information


symbiont-mediated suppression of host JAK-STAT cascade via inhibition of host TYK2 activity / host cell mitochondrion / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT2 activity / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity / viral capsid / ribonucleoside triphosphate phosphatase activity / double-stranded RNA binding / channel activity / monoatomic ion transmembrane transport / clathrin-dependent endocytosis of virus by host cell ...symbiont-mediated suppression of host JAK-STAT cascade via inhibition of host TYK2 activity / host cell mitochondrion / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT2 activity / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity / viral capsid / ribonucleoside triphosphate phosphatase activity / double-stranded RNA binding / channel activity / monoatomic ion transmembrane transport / clathrin-dependent endocytosis of virus by host cell / methyltransferase cap1 activity / mRNA 5'-cap (guanine-N7-)-methyltransferase activity / RNA helicase activity / protein dimerization activity / host cell endoplasmic reticulum membrane / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / serine-type endopeptidase activity / symbiont-mediated activation of host autophagy / viral RNA genome replication / RNA-directed RNA polymerase activity / fusion of virus membrane with host endosome membrane / viral envelope / lipid binding / virion attachment to host cell / host cell nucleus / virion membrane / structural molecule activity / proteolysis / extracellular region / ATP binding / metal ion binding
Similarity search - Function
Flavivirus capsid protein C superfamily / Flavivirus non-structural protein NS2B / Genome polyprotein, Flavivirus / : / Flavivirus non-structural protein NS4A / Flavivirus non-structural protein NS2B / Flavivirus non-structural protein NS4B / mRNA cap 0/1 methyltransferase / Flavivirus non-structural protein NS4B / Flavivirus non-structural protein NS4A ...Flavivirus capsid protein C superfamily / Flavivirus non-structural protein NS2B / Genome polyprotein, Flavivirus / : / Flavivirus non-structural protein NS4A / Flavivirus non-structural protein NS2B / Flavivirus non-structural protein NS4B / mRNA cap 0/1 methyltransferase / 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. / RNA-directed RNA polymerase, thumb domain, Flavivirus / Flavivirus RNA-directed RNA polymerase, thumb domain / RNA-directed RNA polymerase, flavivirus / Flavivirus RNA-directed RNA polymerase, fingers and palm domains / Flavivirus capsid protein C / Flavivirus capsid protein C / Flavivirus non-structural Protein NS1 / Flavivirus non-structural protein NS1 / Envelope glycoprotein M superfamily, flavivirus / Envelope glycoprotein M, flavivirus / Flavivirus polyprotein propeptide superfamily / Flavivirus envelope glycoprotein M / Flavivirus polyprotein propeptide / Flavivirus polyprotein propeptide / : / Flavivirus NS3 helicase, C-terminal helical domain / Flavivirus envelope glycoprotein E, Stem/Anchor domain superfamily / Flavivirus envelope glycoprotein E, stem/anchor domain / Flavivirus envelope glycoprotein E, Stem/Anchor domain / Flaviviral glycoprotein E, central domain, subdomain 1 / Flaviviral glycoprotein E, central domain, subdomain 2 / Flavivirus glycoprotein E, immunoglobulin-like domain / 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 E-set / helicase superfamily c-terminal domain / 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 / RNA-directed RNA polymerase, catalytic domain / RdRp of positive ssRNA viruses catalytic domain profile. / S-adenosyl-L-methionine-dependent methyltransferase superfamily / Peptidase S1, PA clan, chymotrypsin-like fold / Peptidase S1, PA clan / DNA/RNA polymerase superfamily / P-loop containing nucleoside triphosphate hydrolase
Similarity search - Domain/homology
Biological speciesdengue virus type 2
Methodsingle particle reconstruction / cryo EM / Resolution: 3.12 Å
AuthorsZhou QF / Lok SM
Funding support Singapore, 1 items
OrganizationGrant numberCountry
Ministry of Education (MoE, Singapore)MOE-T2EP30122-0002 Singapore
CitationJournal: Nat Commun / Year: 2026
Title: Dynamic structures of dengue virus serotype 2 secreted NS1 and their interactions with heparan sulfate.
Authors: Qunfei Zhou / Thiam-Seng Ng / G Suthershinii / Aaron Wai Kit Tan / Victor A Kostyuchenko / Guntur Fibriansah / Shee-Mei Lok /
Abstract: Dengue secreted non-structural protein 1 (sNS1) contributes to the vascular permeability symptom of severe dengue hemorrhagic fever. Previous flavivirus sNS1 structures suggest that they ...Dengue secreted non-structural protein 1 (sNS1) contributes to the vascular permeability symptom of severe dengue hemorrhagic fever. Previous flavivirus sNS1 structures suggest that they predominantly exist as loose tetramers. Here, we report two stable tetramer structures (3.1-3.6 Å) together with loose tetramers. Formation of the stable tetramers involves a dramatic rearrangement of their N-terminal regions compared to the loose tetramers. We observe a higher molecular weight complex (HMWC) comprising dimeric sNS1 and heat shock proteins, which exhibits much lower endothelial hyperpermeability activity than the tetramer-enriched samples. We also determine high-resolution structures of the sNS1 complex with heparin, an analogue of the attachment factor heparan sulfate, showing that heparin binds to a conserved basic groove on the outer surface of the dimer, at the intra-dimer interface. Pre-incubation of sNS1 with heparin reduces its endothelial hyperpermeability activity. Our findings provide important structural information for future sNS1-based drug or vaccine design.
History
DepositionJul 26, 2025-
Header (metadata) releaseApr 29, 2026-
Map releaseApr 29, 2026-
UpdateApr 29, 2026-
Current statusApr 29, 2026Processing site: PDBj / Status: Released

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Structure visualization

Supplemental images

Downloads & links

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Map

FileDownload / File: emd_65564.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationUnsharpened map
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.67 Å/pix.
x 400 pix.
= 268.4 Å
0.67 Å/pix.
x 400 pix.
= 268.4 Å
0.67 Å/pix.
x 400 pix.
= 268.4 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.671 Å
Density
Contour LevelBy AUTHOR: 0.024
Minimum - Maximum-0.17121653 - 0.2906333
Average (Standard dev.)-0.000010705457 (±0.007479272)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions400400400
Spacing400400400
CellA=B=C: 268.4 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_65564_msk_1.map
Projections & Slices
AxesZYX

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Additional map: The map was sharpened with a global B-factor of -20 Angstrom^2.

Fileemd_65564_additional_1.map
AnnotationThe map was sharpened with a global B-factor of -20 Angstrom^2.
Projections & Slices
AxesZYX

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Density Histograms

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Half map: #2

Fileemd_65564_half_map_1.map
Projections & Slices
AxesZYX

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Half map: #1

Fileemd_65564_half_map_2.map
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Sample components

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Entire : DENV2 non-structural protein 1 complexed with heparin

EntireName: DENV2 non-structural protein 1 complexed with heparin
Components
  • Complex: DENV2 non-structural protein 1 complexed with heparin
    • Protein or peptide: Non-structural protein 1

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Supramolecule #1: DENV2 non-structural protein 1 complexed with heparin

SupramoleculeName: DENV2 non-structural protein 1 complexed with heparin / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: dengue virus type 2 / Strain: PVP94/07

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Macromolecule #1: Non-structural protein 1

MacromoleculeName: Non-structural protein 1 / type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO
Source (natural)Organism: dengue virus type 2 / Strain: PVP94/07
Molecular weightTheoretical: 40.874348 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: DSGCVVSWKN KELKCGSGIF ITDNVHTWTE QYKFQPESPS KLASAIQKAH EEGICGIRSV TRLENLMWKQ ITPELNHILT ENEVKLTIM TGDIKGIMQA GKRSLRPQPT ELKYSWKAWG KAKMLSTELH NHTFLIDGPE TAECPNTNRA WNSLEVEDYG F GVFTTNIW ...String:
DSGCVVSWKN KELKCGSGIF ITDNVHTWTE QYKFQPESPS KLASAIQKAH EEGICGIRSV TRLENLMWKQ ITPELNHILT ENEVKLTIM TGDIKGIMQA GKRSLRPQPT ELKYSWKAWG KAKMLSTELH NHTFLIDGPE TAECPNTNRA WNSLEVEDYG F GVFTTNIW LKLKERQDVF CDSKLMSAAI KDNRAVHADM GYWIESALND TWKIEKASFI EVKSCHWPKS HTLWSNGVLE SE MIIPKNF AGPVSQHNYR PGYHTQTAGP WHLGRLEMDF DFCEGTTVVV TEDCGNRGPS LRTTTASGKL ITEWCCRSCT LPP LRYRGE DGCWYGMEIR PLKEKEENLV NSLVTAHHHH HH

UniProtKB: Genome polyprotein

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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

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 80.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: OTHER / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.2 µm / Nominal defocus min: 1.0 µm / Nominal magnification: 130000
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

CTF correctionSoftware - Name: cryoSPARC / Type: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.12 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 304449
Initial angle assignmentType: RANDOM ASSIGNMENT
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

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