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Molecular basis for GIGYF-Me31B complex assembly in 4EHP-mediated translational repression.

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 ? 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.

SUBMITTER: Peter D

PROVIDER: S-EPMC6771390 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Molecular basis for GIGYF-Me31B complex assembly in 4EHP-mediated translational repression.

Peter Daniel D Ruscica Vincenzo V Bawankar Praveen P Weber Ramona R Helms Sigrun S Valkov Eugene E Igreja Cátia C Izaurralde Elisa E

Genes & development 20190822 19-20

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 com ...[more]

PMID: 31439631

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