7RUP

Structure of the human GIGYF2-TNRC6A complex

Summary for 7RUP

• Entry DOI: 10.2210/pdb7rup/pdb
• Descriptor: GRB10-interacting GYF protein 2, Trinucleotide repeat-containing gene 6A protein, SULFATE ION, ... (4 entities in total)
• Functional Keywords: mirna, 4ehp, translational repression, gene regulation
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 10026.34

Authors

Sobti, M.,Mead, B.J.,Igreja, C.,Stewart, A.G.,Christie, M. (deposition date: 2021-08-18, release date: 2022-08-24, Last modification date: 2024-10-23)

Primary citation

Sobti, M.,Mead, B.J.,Stewart, A.G.,Igreja, C.,Christie, M.
Molecular basis for GIGYF-TNRC6 complex assembly.
Rna, 29:724-734, 2023

PubMed Abstract: The GIGYF proteins interact with 4EHP and RNA-associated proteins to elicit transcript-specific translational repression. However, the mechanism by which the GIGYF1/2-4EHP complex is recruited to its target transcripts remain unclear. Here, we report the crystal structures of the GYF domains from GIGYF1 and GIGYF2 in complex with proline-rich sequences from the miRISC-binding proteins TNRC6C and TNRC6A, respectively. The TNRC6 proline-rich motifs bind to a conserved array of aromatic residues on the surface of the GIGYF1/2 GYF domains, thereby bridging 4EHP to Argonaute-miRNA complexes. Our structures also reveal a phenylalanine residue conserved from yeast to human GYF domains that contributes to GIGYF2 thermostability. The molecular details we outline here are likely to be conserved between GIGYF1/2 and other RNA-binding proteins to elicit 4EHP-mediated repression in different biological contexts.

PubMed: 36854607
DOI: 10.1261/rna.079596.123

Experimental method

X-RAY DIFFRACTION (1.23 Å)