Identification of Nucleolin as an AU-rich Element Binding Protein Involved in bcl-2 mRNA Stabilization
Open Access
- 1 March 2004
- journal article
- Published by Elsevier BV
- Vol. 279 (12), 10855-10863
- https://doi.org/10.1074/jbc.m309111200
Abstract
Amyloids are highly ordered, rigid β-sheet-rich structures that appear to have minimal dynamic flexibility in individual polypeptide chains. Here, we demonstrate that substantial conformational rearrangements occur within mature amyloid fibrils produced from full-length mammalian prion protein. The rearrangement results in a substantial extension of a proteinase K-resistant core and is accompanied by an increase in the β-sheet-rich conformation. The conformational rearrangement was induced in the presence of low concentrations of Triton X-100 either by brief exposure to 80 °C or, with less efficacy, by prolonged incubation at 37 °C at pH 7.5 and is referred to here as “annealing.” Upon annealing, amyloid fibrils acquired a proteinase K-resistant core identical to that found in bovine spongiform encephalopathy-specific scrapie-associated prion protein. Annealing was also observed when amyloid fibrils were exposed to high temperatures in the absence of detergent but in the presence of brain homogenate. These findings suggest that the amyloid fibrils exist in two conformationally distinct states that are separated by a high energy barrier and that yet unknown cellular cofactors may facilitate transition of the fibrils into thermodynamically more stable state. Our studies provide new insight into the complex behavior of prion polymerization and highlight the annealing process, a previously unknown step in the evolution of amyloid structures.Keywords
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