EMD-37423

Single-particle
2.99 Å
EMD-37423 Deposition: 09/09/2023
Map released: 22/05/2024
Last modified: 09/10/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-37423

CryoEM structure of non-structural protein 1 tetramer from ZIKA virus

EMD-37423

Single-particle
2.99 Å
EMD-37423 Deposition: 09/09/2023
Map released: 22/05/2024
Last modified: 09/10/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: dengue virus type 4
Sample: ZIKA virus non-structural protein 1 tetramer
Fitted models: 8wbf (Avg. Q-score: 0.548)

Deposition Authors: Jiao HZ, Pan Q , Hu HL
The step-by-step assembly mechanism of secreted flavivirus NS1 tetramer and hexamer captured at atomic resolution.
Pan Q , Jiao H , Zhang W , Chen Q , Zhang G , Yu J , Zhao W , Hu H
(2024) Sci Adv , 10 , eadm8275 - eadm8275
PUBMED: 38691607
DOI: doi:10.1126/sciadv.adm8275
ISSN: 2375-2548
Abstract:
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.