9IVR

Cryo-EM structure of the CHIKV nsP3 peptide in complex with the NTF2L domain of G3BP1 (Conformation II)

9IVR の概要

• エントリーDOI: 10.2210/pdb9ivr/pdb
• EMDBエントリー: 60933
• 分子名称: Ras GTPase-activating protein-binding protein 1, Polyprotein P1234 (2 entities in total)
• 機能のキーワード: chikungunya virus, nsp3, g3bp1, protein-protein interaction., viral protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 24
• 化学式量合計: 304918.06

構造登録者

Wang, J.,Liu, Y.Z.,Lei, J.,Wang, K.T. (登録日: 2024-07-24, 公開日: 2025-04-09, 最終更新日: 2025-07-16)

主引用文献

Liu, Y.,Wang, J.,Han, Y.,Xia, X.,Zeng, R.,Fan, X.,Zhang, B.,Wang, K.,Lei, J.
Cryo-EM reveals a double oligomeric ring scaffold of the CHIKV nsP3 peptide in complex with the NTF2L domain of host G3BP1.
Mbio, 16:e0396724-e0396724, 2025

PubMed Abstract: Chikungunya virus (CHIKV) poses a severe threat to global public health. The interaction between CHIKV nsP3 and host G3BP1 is critical for viral replication. However, the exact structural mechanism of the nsP3-G3BP1 interaction is scarce. Here, we report a cryo-electron microscopy structure of an octameric-heterotrimer formed by CHIKV nsP3 peptide (designated as CHIKV-43) in complex with the nuclear translocation factor 2-like (NTF2L) domain of G3BP1. The overall structure presents a double-layer ring scaffold. Two FGDF motifs and two alpha helices of CHIKV-43 are essential to bind NTF2L. Particularly, the secondary alpha helix plays key roles in forming the CHIKV-43-NTF2L high-order oligomer. We next analyzed the detailed interactions between CHIKV-43 and the NTF2L domain. The different binding patterns of NTF2L with its various partners were described as well. Subsequently, we demonstrated that the CHIKV-43 peptide is a crucial factor for nsP3 co-localization with G3BP1, reducing stress granule formation and interfering with interferon production. Overall, our findings present the structural and functional mechanisms on CHIKV nsP3 modulating host G3BP1 and provide a potential antiviral target based on the protein-protein interaction interface.

PubMed: 40214262
DOI: 10.1128/mbio.03967-24

実験手法

ELECTRON MICROSCOPY (2.8 Å)