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6s8s

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Extended structure of the human DDX6 C-terminal domain in complex with an EDC3 FDF peptide

Structural highlights

6s8s is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.21Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

DDX6_HUMAN Note=A chromosomal aberration involving DDX6 may be a cause of hematopoietic tumors such as B-cell lymphomas. Translocation t(11;14)(q23;q32).

Function

DDX6_HUMAN In the process of mRNA degradation, may play a role in mRNA decapping.

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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ 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