5DE5: Crystal Structure Of The Complex Between Human Fmrp Rgg Motif And G- Quadruplex Rna

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-A 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-pi interactions, and multiple hydrogen bonds. Many of these interactions critically depend on a type I beta-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.
PDB ID: 5DE5Download
MMDB ID: 132984
PDB Deposition Date: 2015/8/25
Updated in MMDB: 2015/11
Experimental Method:
x-ray diffraction
Resolution: 3  Å
Source Organism:
synthetic construct
Similar Structures:
Biological Unit for 5DE5: dimeric; determined by author and by software (PISA)
Molecular Components in 5DE5
Label Count Molecule
Protein (1 molecule)
Fragile X Mental Retardation Protein 1(Gene symbol: FMR1)
Molecule annotation
Nucleotide(1 molecule)
Molecule annotation
Chemicals (3 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB