5FW5

Crystal structure of human G3BP1 in complex with Semliki Forest Virus nsP3-25 comprising two FGDF motives

Summary for 5FW5

• Entry DOI: 10.2210/pdb5fw5/pdb
• Descriptor: RAS GTPASE-ACTIVATING PROTEIN-BINDING PROTEIN 1, NON-STRUCTURAL PROTEIN 3, SULFATE ION, ... (7 entities in total)
• Functional Keywords: hydrolase, transferase, nonstructural protein 3 (nsp3), ras-gtpase activating protein sh3 domain binding protein g3bp1, rasputin, stress granule associated
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Cytoplasm: Q13283; Non-structural polyprotein: Host endosome membrane; Peripheral membrane protein; Cytoplasmic side. P123: Host endosome membrane; Peripheral membrane protein; Cytoplasmic side. mRNA-capping enzyme nsP1: Host endosome membrane; Peripheral membrane protein; Cytoplasmic side. Protease nsP2: Host endosome membrane ; Peripheral membrane protein ; Cytoplasmic side . Non-structural protein 3: Host endosome membrane; Peripheral membrane protein; Cytoplasmic side. RNA-directed RNA polymerase nsP4: Host endosome membrane; Peripheral membrane protein; Cytoplasmic side: P08411
• Total number of polymer chains: 3
• Total formula weight: 35656.03

Authors

Schulte, T.,Liu, L.,Panas, M.D.,Thaa, B.,Goette, B.,Achour, A.,McInerney, G.M. (deposition date: 2016-02-12, release date: 2016-07-20, Last modification date: 2024-01-10)

Primary citation

Schulte, T.,Liu, L.,Panas, M.D.,Thaa, B.,Dickson, N.,Gotte, B.,Achour, A.,McInerney, G.M.
Combined structural, biochemical and cellular evidence demonstrates that both FGDF motifs in alphavirus nsP3 are required for efficient replication.
Open Biol, 6:-, 2016

PubMed Abstract: Recent findings have highlighted the role of the Old World alphavirus non-structural protein 3 (nsP3) as a host defence modulator that functions by disrupting stress granules, subcellular phase-dense RNA/protein structures formed upon environmental stress. This disruption mechanism was largely explained through nsP3-mediated recruitment of the host G3BP protein via two tandem FGDF motifs. Here, we present the 1.9 Å resolution crystal structure of the NTF2-like domain of G3BP-1 in complex with a 25-residue peptide derived from Semliki Forest virus nsP3 (nsP3-25). The structure reveals a poly-complex of G3BP-1 dimers interconnected through the FGDF motifs in nsP3-25. Although in vitro and in vivo binding studies revealed a hierarchical interaction of the two FGDF motifs with G3BP-1, viral growth curves clearly demonstrated that two intact FGDF motifs are required for efficient viral replication. Chikungunya virus nsP3 also binds G3BP dimers via a hierarchical interaction, which was found to be critical for viral replication. These results highlight a conserved molecular mechanism in host cell modulation.

PubMed: 27383630
DOI: 10.1098/rsob.160078

Experimental method

X-RAY DIFFRACTION (1.92 Å)