title: Production and characterization of RNA aptamers specific for amyloid fibril epitopes.
abstract: One of the most fascinating features of amyloid fibrils is their generic cross-beta architecture that can be formed from many different and completely unrelated proteins. Nonetheless, amyloid fibrils with diverse structural and phenotypic properties can form, both in vivo and in vitro, from the same protein sequence. Here, we have exploited the power of RNA selection techniques to isolate small, structured, single-stranded RNA molecules known as aptamers that were targeted specifically to amyloid-like fibrils formed in vitro from beta(2)-microglobulin (beta(2)m), the amyloid fibril protein associated with dialysis-related amyloidosis. The aptamers bind with high affinity (apparent K(D) approximately nm) to beta(2)m fibrils with diverse morphologies generated under different conditions in vitro, as well as to amyloid fibrils isolated from tissues of dialysis-related amyloidosis patients, demonstrating that they can detect conserved epitopes between different fibrillar species of beta(2)m. Interestingly, the aptamers also recognize some other, but not all, amyloid fibrils generated in vitro or isolated from ex vivo sources. Based on these observations, we have shown that although amyloid fibrils share many common structural properties, they also have features that are unique to individual fibril types.
authors: Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, UK.
authors: David H J
authors: DH
authors: Bunka
authors: Benjamin J
authors: BJ
authors: Mantle
authors: Isobel J
authors: IJ
authors: Morten
authors: Glenys A
authors: GA
authors: Tennent
authors: Sheena E
authors: SE
authors: Radford
authors: Peter G
authors: PG
authors: Stockley
mesh_terms: D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism; D000686:Amyloidosis / Q000378:metabolism; D000818:Animals; D052157:Aptamers, Nucleotide / Q000737:chemistry*; D000939:Epitopes / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D001613:beta 2-Microglobulin / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000682:Amyloid; D052157:Aptamers, Nucleotide; D000939:Epitopes; D001613:beta 2-Microglobulin