6s8r
D. melanogaster RNA helicase Me31B in complex with GIGYF
Structural highlights
FunctionDDX6_DROME ATP-dependent RNA helicase which is a core component of a variety of ribonucleoprotein complexes (RNPs) that play critical roles in translational repression and mRNA decapping during embryogenesis, oogenesis, neurogenesis and neurotransmission (PubMed:11546740, PubMed:16256742, PubMed:17178403, PubMed:18590813, PubMed:21267420, PubMed:21447556, PubMed:28875934, PubMed:28388438, PubMed:17982591). Recruits core components and translational repressors to some RNP complexes, and mediates RNP aggregation into processing granules such as P-bodies (PubMed:28875934, PubMed:11546740, PubMed:16256742, PubMed:17178403, PubMed:21267420, PubMed:21447556, PubMed:17982591). As part of a RNP complex containing tral, eIF4E1, cup, and pAbp, involved in RNP-mediated translational repression of maternal mRNAs during oogenesis and embryogenesis (PubMed:28875934). As part of a RNP complex containing tral and the RNA localization factors exu and yps, mediates translational silencing of mRNAs such as osk/oskar and bcd/bicoid during their transport to the oocyte in order to prevent their translation until they reach their positional destinations (PubMed:11546740). In neurons and possibly imaginal disks, involved in miRNA-mediated translational repression, possibly in association with components of the piRNA transposon silencing pathway (PubMed:21447556, PubMed:17178403, PubMed:21267420, PubMed:17982591, PubMed:21081899). Involved in RNA localization and protein trafficking in the oocyte (PubMed:11546740, PubMed:16256742). As part of an ER-associated RNP containing tral, cup and yps, required for tral-dependent ER exit site formation and consequently efficient trafficking of proteins such as grk and yl through the secretory pathway (PubMed:16256742). Component of neuron RNPs that mediate transport and translation of neuronal RNAs, including translation repression of synaptic transcripts in preparation for their dendritic targeting (PubMed:17178403, PubMed:21267420, PubMed:28388438). As part of the Atx2-Not1 repressor complex promotes Not1-dependent post-transcriptional gene silencing in adult circadian pacemaker neurons in order to sustain high-amplitude circadian rhythms and Pdf cycling in a per-independent manner (PubMed:28388438). Promotes the interaction between Atx2 and Not1 within the Atx2-Not1 RNP complex (PubMed:28388438).[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] Publication Abstract from PubMedGIGYF (Grb10-interacting GYF [glycine-tyrosine-phenylalanine domain]) proteins coordinate with 4EHP (eIF4E [eukaryotic initiation factor 4E] homologous protein), the DEAD (Asp-Glu-Ala-Asp)-box helicase Me31B/DDX6, and mRNA-binding proteins to elicit transcript-specific repression. However, the underlying molecular mechanism remains unclear. Here, we report that GIGYF contains a motif necessary and sufficient for direct interaction with Me31B/DDX6. A 2.4 A crystal structure of the GIGYF-Me31B complex reveals that this motif arranges into a coil connected to a beta hairpin on binding to conserved hydrophobic patches on the Me31B RecA2 domain. Structure-guided mutants indicate that 4EHP-GIGYF-DDX6 complex assembly is required for tristetraprolin-mediated down-regulation of an AU-rich mRNA, thus revealing the molecular principles of translational repression. Molecular basis for GIGYF-Me31B complex assembly in 4EHP-mediated translational repression.,Peter D, Ruscica V, Bawankar P, Weber R, Helms S, Valkov E, Igreja C, Izaurralde E Genes Dev. 2019 Oct 1;33(19-20):1355-1360. doi: 10.1101/gad.329219.119. Epub 2019, Aug 22. PMID:31439631[11] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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