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-Structure paper
タイトル | The step-by-step assembly mechanism of secreted flavivirus NS1 tetramer and hexamer captured at atomic resolution. |
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ジャーナル・号・ページ | Sci Adv, Vol. 10, Issue 18, Page eadm8275, Year 2024 |
掲載日 | 2024年5月3日 |
著者 | Qi Pan / Haizhan Jiao / Wanqin Zhang / Qiang Chen / Geshu Zhang / Jianhai Yu / Wei Zhao / Hongli Hu / |
PubMed 要旨 | 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 ...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. |
リンク | Sci Adv / PubMed:38691607 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.9 - 3.2 Å |
構造データ | EMDB-37419, PDB-8wbb: EMDB-37420, PDB-8wbc: EMDB-37421, PDB-8wbd: EMDB-37422, PDB-8wbe: EMDB-37423, PDB-8wbf: EMDB-37424, PDB-8wbg: EMDB-37425, PDB-8wbh: |
化合物 | ChemComp-TGL: |
由来 |
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キーワード | VIRAL PROTEIN / flavivirus / non-structural protein 1 / dimer |