5DE8

Crystal structure of the complex between human FMRP RGG motif and G-quadruplex RNA, iridium hexammine bound form.

Summary for 5DE8

• Entry DOI: 10.2210/pdb5de8/pdb
• Descriptor: sc1, Fragile X mental retardation protein 1, POTASSIUM ION, ... (4 entities in total)
• Functional Keywords: fragile x syndrome, rna structure, rgg box, fmrp, g-quadruplex, rna binding protein-rna complex, rna binding protein/rna
• Biological source: synthetic construct; More
• Total number of polymer chains: 4
• Total formula weight: 28047.72

Authors

Vasilyev, N.,Polonskaia, A.,Darnell, J.C.,Darnell, R.B.,Patel, D.J.,Serganov, A. (deposition date: 2015-08-25, release date: 2015-09-23, Last modification date: 2024-03-06)

Primary citation

Vasilyev, N.,Polonskaia, A.,Darnell, J.C.,Darnell, R.B.,Patel, D.J.,Serganov, A.
Crystal structure reveals specific recognition of a G-quadruplex RNA by a beta-turn in the RGG motif of FMRP.
Proc.Natl.Acad.Sci.USA, 112:E5391-E5400, 2015

PubMed Abstract: Fragile X Mental Retardation Protein (FMRP) is a regulatory RNA binding protein that plays a central role in the development of several human disorders including Fragile X Syndrome (FXS) and autism. FMRP uses an arginine-glycine-rich (RGG) motif for specific interactions with guanine (G)-quadruplexes, mRNA elements implicated in the disease-associated regulation of specific mRNAs. Here we report the 2.8-Å crystal structure of the complex between the human FMRP RGG peptide bound to the in vitro selected G-rich RNA. In this model system, the RNA adopts an intramolecular K(+)-stabilized G-quadruplex structure composed of three G-quartets and a mixed tetrad connected to an RNA duplex. The RGG peptide specifically binds to the duplex-quadruplex junction, the mixed tetrad, and the duplex region of the RNA through shape complementarity, cation-π interactions, and multiple hydrogen bonds. Many of these interactions critically depend on a type I β-turn, a secondary structure element whose formation was not previously recognized in the RGG motif of FMRP. RNA mutagenesis and footprinting experiments indicate that interactions of the peptide with the duplex-quadruplex junction and the duplex of RNA are equally important for affinity and specificity of the RGG-RNA complex formation. These results suggest that specific binding of cellular RNAs by FMRP may involve hydrogen bonding with RNA duplexes and that RNA duplex recognition can be a characteristic RNA binding feature for RGG motifs in other proteins.

PubMed: 26374839
DOI: 10.1073/pnas.1515737112

Experimental method

X-RAY DIFFRACTION (3.1003 Å)