Amyloid fibrils from the mammalian protein prothymosin α

Abstract
Mammalian prothymosin α, a small (12 kDa) and extremely acidic protein (pI 3.5), is a member of the growing family of ‘natively’ unfolded proteins. We demonstrate that at low pH (∼3) and high concentrations, prothymosin α is capable of forming regular elongated fibrils with flat ribbon structure 4–5 nm in height and 12–13 nm in width as judged from scanning force and electron microscopy. These aggregates induced a characteristic spectral shift of thioflavin T fluorescence and their circular dichroism spectra were indicative of significant β-sheet content, suggesting formation of classical amyloid. Our findings indicate that natively unfolded proteins may have a general propensity to form amyloid fibrils under conditions inducing partially folded conformations

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