Publication

Article Metrics

Citations


Online attention

GIGYF1/2 proteins use auxiliary sequences to selectively bind to 4EHP and repress target mRNA expression

DOI: 10.1101/gad.299420.117 DOI Help

Authors: Daniel Peter (Max Planck Institute for Developmental Biology) , Ramona Weber (Max Planck Institute for Developmental Biology) , Felix Sandmeir (Max Planck Institute for Developmental Biology) , Lara Wohlbold (Max Planck Institute for Developmental Biology) , Sigrun Helms (Max Planck Institute for Developmental Biology) , Praveen Bawankar (Max Planck Institute for Developmental Biology) , Eugene Valkov (Max Planck Institute for Developmental Biology) , Cátia Igreja (Max Planck Institute for Developmental Biology) , Elisa Izaurralde (Max Planck Institute for Developmental Biology)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Genes & Development , VOL 31 , PAGES 1147 - 1161

State: Published (Approved)
Published: July 2017
Diamond Proposal Number(s): 13715

Open Access Open Access

Abstract: The eIF4E homologous protein (4EHP) is thought to repress translation by competing with eIF4E for binding to the 5′ cap structure of specific mRNAs to which it is recruited through interactions with various proteins, including the GRB10-interacting GYF (glycine–tyrosine–phenylalanine domain) proteins 1 and 2 (GIGYF1/2). Despite its similarity to eIF4E, 4EHP does not interact with eIF4G and therefore fails to initiate translation. In contrast to eIF4G, GIGYF1/2 bind selectively to 4EHP but not eIF4E. Here, we present crystal structures of the 4EHP-binding regions of GIGYF1 and GIGYF2 in complex with 4EHP, which reveal the molecular basis for the selectivity of the GIGYF1/2 proteins for 4EHP. Complementation assays in a GIGYF1/2-null cell line using structure-based mutants indicate that 4EHP requires interactions with GIGYF1/2 to down-regulate target mRNA expression. Our studies provide structural insights into the assembly of 4EHP–GIGYF1/2 repressor complexes and reveal that rather than merely facilitating 4EHP recruitment to transcripts, GIGYF1/2 proteins are required for repressive activity.

Journal Keywords: eIF4E; translational regulation; translational repression

Subject Areas: Biology and Bio-materials


Instruments: B21-High Throughput SAXS

Other Facilities: PX at Swiss Light Source; SWING at SOLEIL

Added On: 31/10/2017 12:27

Documents:
1147.full.pdf

Discipline Tags:

Life Sciences & Biotech Genetics Structural biology

Technical Tags:

Scattering Small Angle X-ray Scattering (SAXS)