Structural highlights
Function
GGYF1_HUMAN May act cooperatively with GRB10 to regulate tyrosine kinase receptor signaling. May increase IGF1 receptor phosphorylation under IGF1 stimulation as well as phosphorylation of IRS1 and SHC1 (By similarity).[1]
Publication Abstract from PubMed
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 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 domain, 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.
Molecular basis for GIGYF-TNRC6 complex assembly.,Sobti M, Mead BJ, Stewart AG, Igreja C, Christie M RNA. 2023 Feb 28:rna.079596.123. doi: 10.1261/rna.079596.123. PMID:36854607[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Giovannone B, Lee E, Laviola L, Giorgino F, Cleveland KA, Smith RJ. Two novel proteins that are linked to insulin-like growth factor (IGF-I) receptors by the Grb10 adapter and modulate IGF-I signaling. J Biol Chem. 2003 Aug 22;278(34):31564-73. Epub 2003 May 27. PMID:12771153 doi:http://dx.doi.org/10.1074/jbc.M211572200
- ↑ Sobti M, Mead BJ, Stewart AG, Igreja C, Christie M. Molecular basis for GIGYF-TNRC6 complex assembly. RNA. 2023 Feb 28:rna.079596.123. PMID:36854607 doi:10.1261/rna.079596.123
