6S8S

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

Summary for 6S8S

• Entry DOI: 10.2210/pdb6s8s/pdb
• Descriptor: Probable ATP-dependent RNA helicase DDX6, Enhancer of mRNA-decapping protein 3, PHOSPHATE ION, ... (5 entities in total)
• Functional Keywords: translational control, mrna decay, mirna, rna binding protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 57051.50

Authors

Peter, D.,Valkov, E. (deposition date: 2019-07-10, release date: 2019-09-04, Last modification date: 2024-01-24)

Primary citation

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., 33:1355-1360, 2019

PubMed Abstract: 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 Å crystal structure of the GIGYF-Me31B complex reveals that this motif arranges into a coil connected to a β 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.

PubMed: 31439631
DOI: 10.1101/gad.329219.119

Experimental method

X-RAY DIFFRACTION (2.21 Å)