2RSK

RNA aptamer against prion protein in complex with the partial binding peptide

2RSK の概要

• エントリーDOI: 10.2210/pdb2rsk/pdb
• 分子名称: RNA (5'-R(*GP*GP*AP*GP*GP*AP*GP*GP*AP*GP*GP*A)-3'), partial binding peptide of Major prion protein (2 entities in total)
• 機能のキーワード: aptamer, prion, rna, alzheimer's disease, membrane protein-rna complex, membrane protein/rna
• 由来する生物種: Bos taurus (Bovine)
• 細胞内の位置: Cell membrane; Lipid-anchor, GPI-anchor (By similarity): P10279
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 10842.15

構造登録者

Mashima, T.,Nishikawa, F.,Kamatari, Y.O.,Fujiwara, H.,Nishikawa, S.,Kuwata, K.,Katahira, M. (登録日: 2012-03-08, 公開日: 2013-02-13, 最終更新日: 2024-05-15)

主引用文献

Mashima, T.,Nishikawa, F.,Kamatari, Y.O.,Fujiwara, H.,Saimura, M.,Nagata, T.,Kodaki, T.,Nishikawa, S.,Kuwata, K.,Katahira, M.
Anti-prion activity of an RNA aptamer and its structural basis
Nucleic Acids Res., 41:1355-1362, 2013

PubMed Abstract: Prion proteins (PrPs) cause prion diseases, such as bovine spongiform encephalopathy. The conversion of a normal cellular form (PrP(C)) of PrP into an abnormal form (PrP(Sc)) is thought to be associated with the pathogenesis. An RNA aptamer that tightly binds to and stabilizes PrP(C) is expected to block this conversion and to thereby prevent prion diseases. Here, we show that an RNA aptamer comprising only 12 residues, r(GGAGGAGGAGGA) (R12), reduces the PrP(Sc) level in mouse neuronal cells persistently infected with the transmissible spongiform encephalopathy agent. Nuclear magnetic resonance analysis revealed that R12, folded into a unique quadruplex structure, forms a dimer and that each monomer simultaneously binds to two portions of the N-terminal half of PrP(C), resulting in tight binding. Electrostatic and stacking interactions contribute to the affinity of each portion. Our results demonstrate the therapeutic potential of an RNA aptamer as to prion diseases.

PubMed: 23180780
DOI: 10.1093/nar/gks1132

実験手法

SOLUTION NMR