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J. Biol. Chem., Vol. 282, Issue 47, 34500-34509, November 23, 2007

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Production and Characterization of RNA Aptamers Specific for Amyloid Fibril Epitopes^*

David H. J. Bunka, Benjamin J. Mantle, Isobel J. Morten, Glenys A. Tennent, Sheena E. Radford¹, and Peter G. Stockley²

From the Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT and the Centre for Amyloidosis and Acute Phase Proteins, Hampstead Campus, University College London, London NW3 2PF, United Kingdom

One of the most fascinating features of amyloid fibrils is their generic cross- 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 ₂-microglobulin (₂m), the amyloid fibril protein associated with dialysis-related amyloidosis. The aptamers bind with high affinity (apparent K_D nM) to ₂m 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 ₂m. 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.

Received for publication, May 3, 2007 , and in revised form, August 28, 2007.

^* This work was supported by grants from the United Kingdom Medical Research Council, Biotechnology & Biological Sciences Research Council, and The Wellcome Trust. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1-S4 and Table S1.

¹ To whom correspondence may be addressed. Tel.: 0113-343-3170; Fax: 0113-343-7486; E-mail: s.e.radford{at}leeds.ac.uk.

² To whom correspondence may be addressed. Tel.: 0113-343-3092; Fax: 0113-343-7897; E-mail: stockley{at}bmb.leeds.ac.uk.

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