Molecular basis for GIGYF–Me31B complex assembly in 4EHP-mediated translational repression
- Daniel Peter1,2,4,
- Vincenzo Ruscica1,4,
- Praveen Bawankar1,3,4,
- Ramona Weber1,
- Sigrun Helms1,
- Eugene Valkov1,
- Cátia Igreja1 and
- Elisa Izaurralde1,5
- 1Department of Biochemistry, Max Planck Institute for Developmental Biology, D-72076 Tübingen, Germany;
- 2European Molecular Biology Laboratory, 38042 Grenoble Cedex 9, France;
- 3Institute of Molecular Biology, 55128 Mainz, Germany
- Corresponding authors: catia.igreja{at}tuebingen.mpg.de, eugene.valkov{at}tuebingen.mpg.de
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↵4 These authors contributed equally to this work.
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.
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Footnotes
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Supplemental material is available for this article.
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Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.329219.119.
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Freely available online through the Genes & Development Open Access option.
- Received May 28, 2019.
- Accepted July 18, 2019.
This article, published in Genes & Development, is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.