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A folded and functional protein domain in an amyloid-like fibril

¹ Institut für Biochemie und Biotechnologie, Martin-Luther-Universität Halle-Wittenberg, 06120 Halle, Germany
² Biozentrum der Martin-Luther-Universität Halle-Wittenberg, Weinbergweg 22, 06120 Halle, Germany
³ Roche Diagnostics GmbH, 82372 Penzberg, Germany
⁴ Biochemisches Laboratorium, Universität Bayreuth, 95440 Bayreuth, Germany

(RECEIVED October 2, 2007; FINAL REVISION February 26, 2008; ACCEPTED February 26, 2008)

The effect of the polypeptide environment on polyalanine-induced fibril formation was investigated with amyloidogenic fragments from PAPBN1, a nuclear protein controlling polyadenylation. Mutation-caused extensions of the natural 10 alanine sequence up to maximally 17 alanines result in fibril formation of PABPN1 and the development of the disease oculopharyngeal muscular dystrophy (OPMD). We explored the influence of fibril formation on the structure and function of a one-domain protein linked to the fibril-forming part of PABPN1. The well-characterized, stably folded, one-domain protein, cold-shock protein CspB from Bacillus subtilis, was fused either to the C terminus of the entire N-terminal domain of PABPN1 or directly to peptides consisting of 10 or 17 alanine residues. The fusion protein between the N-terminal domain of PABPN1 and CspB formed fibrils in which the structure and activity of CspB were retained. In the fibrils formed by fusions in which the polyalanine sequence was directly linked to CspB, CspB was unfolded. These results indicate that the folded conformation and the function of a protein domain can be maintained in amyloid-like fibrils, and that the distance between this domain and the fibril plays an important role.

Keywords: polyalanine; fibril formation; CspB; PABPN1; protein folding

Article published online ahead of print. Article and publication date are at http://www.proteinscience.org/cgi/doi/10.1110/ps.073276308.

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