9J5S

Crystal structure of human G3BP1 in complex with CHIKV nsP3 peptide

Summary for 9J5S

• Entry DOI: 10.2210/pdb9j5s/pdb
• Descriptor: Ras GTPase-activating protein-binding protein 1, Polyprotein P1234 (2 entities in total)
• Functional Keywords: chikungunya virus, non-structural protein, virus-host interaction, viral protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 37842.61

Authors

Liu, Y.Z.,Lei, J. (deposition date: 2024-08-13, release date: 2025-04-09, Last modification date: 2025-06-25)

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: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

Experimental method

X-RAY DIFFRACTION (2.84 Å)