9IVR

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

Summary for 9IVR

• Entry DOI: 10.2210/pdb9ivr/pdb
• EMDB information: 60933
• Descriptor: Ras GTPase-activating protein-binding protein 1, Polyprotein P1234 (2 entities in total)
• Functional Keywords: chikungunya virus, nsp3, g3bp1, protein-protein interaction., viral protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 24
• Total formula weight: 304918.06

Authors

Wang, J.,Liu, Y.Z.,Lei, J.,Wang, K.T. (deposition date: 2024-07-24, release date: 2025-04-09, Last modification date: 2025-05-28)

Primary citation

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:-, 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

Experimental method

ELECTRON MICROSCOPY (2.8 Å)