2. Academic Validation
  3. Molecular basis for GIGYF-Me31B complex assembly in 4EHP-mediated translational repression

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.
Daniel Peter # 1 2,  Vincenzo Ruscica # 1,  Praveen Bawankar # 1 3,  Ramona Weber 1,  Sigrun Helms 1,  Eugene Valkov 1,  Cátia Igreja 1,  Elisa Izaurralde 1
Affiliations

Affiliations

  • 1 Department of Biochemistry, Max Planck Institute for Developmental Biology, D-72076 Tübingen, Germany.
  • 2 European Molecular Biology Laboratory, 38042 Grenoble Cedex 9, France.
  • 3 Institute of Molecular Biology, 55128 Mainz, Germany.
  • # Contributed equally.
PMID: 31439631 DOI: 10.1101/gad.329219.119
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.

Keywords

DEAD-box helicases; RNA regulation; translational repression.

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