8WBC

CryoEM structure of non-structural protein 1 tetramer from dengue virus type 4

8WBC の概要

• エントリーDOI: 10.2210/pdb8wbc/pdb
• EMDBエントリー: 37420
• 分子名称: Genome polyprotein (1 entity in total)
• 機能のキーワード: flavivirus, non-structural protein 1, viral protein
• 由来する生物種: Dengue virus 4 Philippines/H241/1956
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 161979.03

構造登録者

Jiao, H.Z.,Pan, Q.,Hu, H.L. (登録日: 2023-09-09, 公開日: 2024-05-22, 最終更新日: 2024-11-13)

主引用文献

Pan, Q.,Jiao, H.,Zhang, W.,Chen, Q.,Zhang, G.,Yu, J.,Zhao, W.,Hu, H.
The step-by-step assembly mechanism of secreted flavivirus NS1 tetramer and hexamer captured at atomic resolution.
Sci Adv, 10:eadm8275-eadm8275, 2024

PubMed 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.

PubMed: 38691607
DOI: 10.1126/sciadv.adm8275

実験手法

ELECTRON MICROSCOPY (3.03 Å)