5DEA

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

5DEA の概要

• エントリーDOI: 10.2210/pdb5dea/pdb
• 分子名称: sc1, Fragile X mental retardation protein 1, POTASSIUM ION, ... (5 entities in total)
• 機能のキーワード: fragile x syndrome, rna structure, rgg box, fmrp, g-quadruplex, rna binding protein-rna complex, rna binding protein/rna
• 由来する生物種: synthetic construct; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 27052.63

構造登録者

Vasilyev, N.,Polonskaia, A.,Darnell, J.C.,Darnell, R.B.,Patel, D.J.,Serganov, A. (登録日: 2015-08-25, 公開日: 2015-09-23, 最終更新日: 2023-09-27)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.7973 Å)