7SUO
Crystal Structure of the G3BP1 NTF2-like domain bound to the IDR1 of SARS-CoV-2 nucleocapsid protein
Summary for 7SUO
| Entry DOI | 10.2210/pdb7suo/pdb |
| Descriptor | Ras GTPase-activating protein-binding protein 1, Nucleoprotein (3 entities in total) |
| Functional Keywords | nucleocapsid protein, g3bp1, hydrolase-viral protein complex, hydrolase/viral protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 33772.20 |
| Authors | Biswal, M.,Lu, J.,Song, J. (deposition date: 2021-11-17, release date: 2022-03-16, Last modification date: 2023-10-18) |
| Primary citation | Biswal, M.,Lu, J.,Song, J. SARS-CoV-2 Nucleocapsid Protein Targets a Conserved Surface Groove of the NTF2-like Domain of G3BP1. J.Mol.Biol., 434:167516-167516, 2022 Cited by PubMed Abstract: Stress granule (SG) formation mediated by Ras GTPase-activating protein-binding protein 1 (G3BP1) constitutes a key obstacle for viral replication, which makes G3BP1 a frequent target for viruses. For instance, the SARS-CoV-2 nucleocapsid (N) protein interacts with G3BP1 directly to suppress SG assembly and promote viral production. However, the molecular basis for the SARS-CoV-2 N - G3BP1 interaction remains elusive. Here we report biochemical and structural analyses of the SARS-CoV-2 N - G3BP1 interaction, revealing differential contributions of various regions of SARS-CoV-2 N to G3BP1 binding. The crystal structure of the NTF2-like domain of G3BP1 (G3BP1) in complex with a peptide derived from SARS-CoV-2 N (residues 1-25, N) reveals that SARS-CoV-2 N occupies a conserved surface groove of G3BP1 via surface complementarity. We show that a φ-x-F (φ, hydrophobic residue) motif constitutes the primary determinant for G3BP1-targeting proteins, while the flanking sequence underpins diverse secondary interactions. We demonstrate that mutation of key interaction residues of the SARS-CoV-2 N - G3BP1 complex leads to disruption of the SARS-CoV-2 N - G3BP1 interaction in vitro. Together, these results provide a molecular basis of the strain-specific interaction between SARS-CoV-2 N and G3BP1, which has important implications for the development of novel therapeutic strategies against SARS-CoV-2 infection. PubMed: 35240128DOI: 10.1016/j.jmb.2022.167516 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.35 Å) |
Structure validation
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