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TitleThe step-by-step assembly mechanism of secreted flavivirus NS1 tetramer and hexamer captured at atomic resolution.
Journal, issue, pagesSci Adv, Vol. 10, Issue 18, Page eadm8275, Year 2024
Publish dateMay 3, 2024
AuthorsQi Pan / Haizhan Jiao / Wanqin Zhang / Qiang Chen / Geshu Zhang / Jianhai Yu / Wei Zhao / Hongli Hu /
PubMed AbstractFlaviviruses encode a conserved, membrane-associated nonstructural protein 1 (NS1) with replication and immune evasion functions. The current knowledge of secreted NS1 (sNS1) oligomers is based on ...Flaviviruses encode a conserved, membrane-associated nonstructural protein 1 (NS1) with replication and immune evasion functions. The current knowledge of secreted NS1 (sNS1) oligomers is based on several low-resolution structures, thus hindering the development of drugs and vaccines against flaviviruses. Here, we revealed that recombinant sNS1 from flaviviruses exists in a dynamic equilibrium of dimer-tetramer-hexamer states. Two DENV4 hexameric NS1 structures and several tetrameric NS1 structures from multiple flaviviruses were solved at atomic resolution by cryo-EM. The stacking of the tetrameric NS1 and hexameric NS1 is facilitated by the hydrophobic β-roll and connector domains. Additionally, a triacylglycerol molecule located within the central cavity may play a role in stabilizing the hexamer. Based on differentiated interactions between the dimeric NS1, two distinct hexamer models (head-to-head and side-to-side hexamer) and the step-by-step assembly mechanisms of NS1 dimer into hexamer were proposed. We believe that our study sheds light on the understanding of the NS1 oligomerization and contributes to NS1-based therapies.
External linksSci Adv / PubMed:38691607 / PubMed Central
MethodsEM (single particle)
Resolution2.9 - 3.2 Å
Structure data

37419

8wbb

EMDB-37419, PDB-8wbb:
CryoEM structure of non-structural protein 1 dimer from dengue virus type 4
Method: EM (single particle) / Resolution: 2.9 Å

37420

8wbc

EMDB-37420, PDB-8wbc:
CryoEM structure of non-structural protein 1 tetramer from dengue virus type 4
Method: EM (single particle) / Resolution: 3.03 Å

37421

8wbd

EMDB-37421, PDB-8wbd:
CryoEM structure of non-structural protein 1 hexamer 1 from dengue virus type 4
Method: EM (single particle) / Resolution: 2.9 Å

37422

8wbe

EMDB-37422, PDB-8wbe:
CryoEM structure of non-structural protein 1 hexamer 2 from dengue virus type 4
Method: EM (single particle) / Resolution: 3.0 Å

37423

8wbf

EMDB-37423, PDB-8wbf:
CryoEM structure of non-structural protein 1 tetramer from ZIKA virus
Method: EM (single particle) / Resolution: 2.99 Å

37424

8wbg

EMDB-37424, PDB-8wbg:
CryoEM structure of non-structural protein 1 tetramer from ZIKA virus
Method: EM (single particle) / Resolution: 3.2 Å

37425

8wbh

EMDB-37425, PDB-8wbh:
CryoEM structure of non-structural protein 1 tetramer from Japanese encephalitis virus
Method: EM (single particle) / Resolution: 3.2 Å

Chemicals

ChemComp-TGL:
TRISTEAROYLGLYCEROL / Stearin

Source
  • dengue virus type 4
  • dengue virus 4 philippines/h241/1956
  • japanese encephalitis virus
KeywordsVIRAL PROTEIN / flavivirus / non-structural protein 1 / dimer

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