title: Unique quadruplex structure and interaction of an RNA aptamer against bovine prion protein.
abstract: RNA aptamers against bovine prion protein (bPrP) were obtained, most of the obtained aptamers being found to contain the r(GGAGGAGGAGGA) (R12) sequence. Then, it was revealed that R12 binds to both bPrP and its beta-isoform with high affinity. Here, we present the structure of R12. This is the first report on the structure of an RNA aptamer against prion protein. R12 forms an intramolecular parallel quadruplex. The quadruplex contains G:G:G:G tetrad and G(:A):G:G(:A):G hexad planes. Two quadruplexes form a dimer through intermolecular hexad-hexad stacking. Two lysine clusters of bPrP have been identified as binding sites for R12. The electrostatic interaction between the uniquely arranged phosphate groups of R12 and the lysine clusters is suggested to be responsible for the affinity of R12 to bPrP. The stacking interaction between the G:G:G:G tetrad planes and tryptophan residues may also contribute to the affinity. One R12 dimer molecule is supposed to simultaneously bind the two lysine clusters of one bPrP molecule, resulting in even higher affinity. The atomic coordinates of R12 would be useful for the development of R12 as a therapeutic agent against prion diseases and Alzheimer's disease.
authors: Department of Supramolecular Biology, Graduate School of Nanobioscience, Yokohama City University, 1-7-29 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan.
authors: Tsukasa
authors: T
authors: Mashima
authors: Akimasa
authors: A
authors: Matsugami
authors: Fumiko
authors: F
authors: Nishikawa
authors: Satoshi
authors: S
authors: Nishikawa
authors: Masato
authors: M
authors: Katahira
mesh_terms: D000818:Animals; D052157:Aptamers, Nucleotide / Q000737:chemistry*; D001665:Binding Sites; D002417:Cattle; D019281:Dimerization; D054856:G-Quadruplexes; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D011328:Prions / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism
chemical_list: D052157:Aptamers, Nucleotide; D011328:Prions