5fw5
Crystal structure of human G3BP1 in complex with Semliki Forest Virus nsP3-25 comprising two FGDF motives
Structural highlights
FunctionG3BP1_HUMAN May be a regulated effector of stress granule assembly. Phosphorylation-dependent sequence-specific endoribonuclease in vitro. Cleaves exclusively between cytosine and adenine and cleaves MYC mRNA preferentially at the 3'-UTR. ATP- and magnesium-dependent helicase. Unwinds preferentially partial DNA and RNA duplexes having a 17 bp annealed portion and either a hanging 3' tail or hanging tails at both 5'- and 3'-ends. Unwinds DNA/DNA, RNA/DNA, and RNA/RNA substrates with comparable efficiency. Acts unidirectionally by moving in the 5' to 3' direction along the bound single-stranded DNA.[1] [2] Publication Abstract from PubMedRecent 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 A 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. Combined structural, biochemical and cellular evidence demonstrates that both FGDF motifs in alphavirus nsP3 are required for efficient replication.,Schulte T, Liu L, Panas MD, Thaa B, Dickson N, Gotte B, Achour A, McInerney GM Open Biol. 2016 Jul;6(7). pii: 160078. doi: 10.1098/rsob.160078. PMID:27383630[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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