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TitleDynamic structures of dengue virus serotype 2 secreted NS1 and their interactions with heparan sulfate.
Journal, issue, pagesNat Commun, Vol. 17, Issue 1, Year 2026
Publish dateApr 15, 2026
AuthorsQunfei Zhou / Thiam-Seng Ng / G Suthershinii / Aaron Wai Kit Tan / Victor A Kostyuchenko / Guntur Fibriansah / Shee-Mei Lok /
PubMed AbstractDengue 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.
External linksNat Commun / PubMed:41986350 / PubMed Central
MethodsEM (single particle)
Resolution3.12 - 6.1 Å
Structure data

65558

9w1x

EMDB-65558, PDB-9w1x:
DENV2 non-structural protein 1 (NS1) Loose Tetramer Conformation 2
Method: EM (single particle) / Resolution: 4.6 Å

65559

9w1y

EMDB-65559, PDB-9w1y:
DENV2 non-structural protein 1 (NS1) with C-terminal mVenus Conformation 2
Method: EM (single particle) / Resolution: 6.1 Å

65560

9w1z

EMDB-65560, PDB-9w1z:
DENV2 non-structural protein 1 (NS1) Stable Tetramer Conformation 2
Method: EM (single particle) / Resolution: 3.14 Å

65561

9w20

EMDB-65561, PDB-9w20:
DENV2 non-structural protein 1 (NS1) Stable Tetramer Conformation 1
Method: EM (single particle) / Resolution: 3.63 Å

65562

9w21

EMDB-65562, PDB-9w21:
DENV2 non-structural protein 1 (NS1) Loose Tetramer Conformation 1
Method: EM (single particle) / Resolution: 4.7 Å

65563

9w22

EMDB-65563, PDB-9w22:
DENV2 non-structural protein 1 (NS1) Dimer
Method: EM (single particle) / Resolution: 3.12 Å

65564

9w23

EMDB-65564, PDB-9w23:
DENV2 non-structural protein 1 (NS1) Stable Tetramer complexed with Heparin
Method: EM (single particle) / Resolution: 3.12 Å

65565

9w24

EMDB-65565, PDB-9w24:
DENV2 non-structural protein 1 (NS1) with C-terminal mVenus fusion
Method: EM (single particle) / Resolution: 3.8 Å

65566

9w25

EMDB-65566, PDB-9w25:
DENV2 non-structural protein 1 (NS1) with C-terminal mVenus Conformation 1
Method: EM (single particle) / Resolution: 5.3 Å

Source
  • dengue virus type 2
  • aequorea victoria (jellyfish)
KeywordsVIRAL PROTEIN / Dengue virus; non-structural protein 1; flavivirus; NS1 / Dengue virus; non-structural protein 1; flavivirus; mVenus / Dengue virus; non-structural protein 1; NS1; flavivirus / Dengue virus; non-structural protein 1; recombinant; dimer / Dengue virus; non-structural protein 1; flavivirus; heparin

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