6s8r

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D. melanogaster RNA helicase Me31B in complex with GIGYFD. melanogaster RNA helicase Me31B in complex with GIGYF

Structural highlights

6s8r is a 2 chain structure with sequence from Drosophila melanogaster. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.41Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

DDX6_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 PubMed

GIGYF (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

  1. Nakamura A, Amikura R, Hanyu K, Kobayashi S. Me31B silences translation of oocyte-localizing RNAs through the formation of cytoplasmic RNP complex during Drosophila oogenesis. Development. 2001 Sep;128(17):3233-42. PMID:11546740
  2. Wilhelm JE, Buszczak M, Sayles S. Efficient protein trafficking requires trailer hitch, a component of a ribonucleoprotein complex localized to the ER in Drosophila. Dev Cell. 2005 Nov;9(5):675-85. doi: 10.1016/j.devcel.2005.09.015. PMID:16256742 doi:http://dx.doi.org/10.1016/j.devcel.2005.09.015
  3. Barbee SA, Estes PS, Cziko AM, Hillebrand J, Luedeman RA, Coller JM, Johnson N, Howlett IC, Geng C, Ueda R, Brand AH, Newbury SF, Wilhelm JE, Levine RB, Nakamura A, Parker R, Ramaswami M. Staufen- and FMRP-containing neuronal RNPs are structurally and functionally related to somatic P bodies. Neuron. 2006 Dec 21;52(6):997-1009. doi: 10.1016/j.neuron.2006.10.028. PMID:17178403 doi:http://dx.doi.org/10.1016/j.neuron.2006.10.028
  4. Hillebrand J, Barbee SA, Ramaswami M. P-body components, microRNA regulation, and synaptic plasticity. ScientificWorldJournal. 2007 Nov 2;7:178-90. doi: 10.1100/tsw.2007.206. PMID:17982591 doi:http://dx.doi.org/10.1100/tsw.2007.206
  5. Thomson T, Liu N, Arkov A, Lehmann R, Lasko P. Isolation of new polar granule components in Drosophila reveals P body and ER associated proteins. Mech Dev. 2008 Sep-Oct;125(9-10):865-73. doi: 10.1016/j.mod.2008.06.005. Epub, 2008 Jun 12. PMID:18590813 doi:http://dx.doi.org/10.1016/j.mod.2008.06.005
  6. Jeske M, Moritz B, Anders A, Wahle E. Smaug assembles an ATP-dependent stable complex repressing nanos mRNA translation at multiple levels. EMBO J. 2011 Jan 5;30(1):90-103. doi: 10.1038/emboj.2010.283. Epub 2010 Nov 16. PMID:21081899 doi:http://dx.doi.org/10.1038/emboj.2010.283
  7. Hillebrand J, Pan K, Kokaram A, Barbee S, Parker R, Ramaswami M. The Me31B DEAD-Box Helicase Localizes to Postsynaptic Foci and Regulates Expression of a CaMKII Reporter mRNA in Dendrites of Drosophila Olfactory Projection Neurons. Front Neural Circuits. 2010 Nov 3;4:121. doi: 10.3389/fncir.2010.00121., eCollection 2010. PMID:21267420 doi:http://dx.doi.org/10.3389/fncir.2010.00121
  8. Liu L, Qi H, Wang J, Lin H. PAPI, a novel TUDOR-domain protein, complexes with AGO3, ME31B and TRAL in the nuage to silence transposition. Development. 2011 May;138(9):1863-73. doi: 10.1242/dev.059287. Epub 2011 Mar 29. PMID:21447556 doi:http://dx.doi.org/10.1242/dev.059287
  9. Lee J, Yoo E, Lee H, Park K, Hur JH, Lim C. LSM12 and ME31B/DDX6 Define Distinct Modes of Posttranscriptional Regulation by ATAXIN-2 Protein Complex in Drosophila Circadian Pacemaker Neurons. Mol Cell. 2017 Apr 6;66(1):129-140.e7. doi: 10.1016/j.molcel.2017.03.004. PMID:28388438 doi:http://dx.doi.org/10.1016/j.molcel.2017.03.004
  10. Wang M, Ly M, Lugowski A, Laver JD, Lipshitz HD, Smibert CA, Rissland OS. ME31B globally represses maternal mRNAs by two distinct mechanisms during the Drosophila maternal-to-zygotic transition. Elife. 2017 Sep 6;6. pii: 27891. doi: 10.7554/eLife.27891. PMID:28875934 doi:http://dx.doi.org/10.7554/eLife.27891
  11. Peter D, Ruscica V, Bawankar P, Weber R, Helms S, Valkov E, Igreja C, Izaurralde E. Molecular basis for GIGYF-Me31B complex assembly in 4EHP-mediated translational repression. Genes Dev. 2019 Oct 1;33(19-20):1355-1360. doi: 10.1101/gad.329219.119. Epub 2019, Aug 22. PMID:31439631 doi:http://dx.doi.org/10.1101/gad.329219.119

6s8r, resolution 2.41Å

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