Abstract
Amyloid beta (Aβ) protein in Alzheimers disease and scrapie prion protein (PrPsc) in Scrapie is the key component of amyloid plaques in brain whereas stefin B is an intracellular cysteine proteinase inhibitor, broadly distributed in different tissue and recently reported to form amyloid fibrils in vitro. By reducing the pH to around 4.6, the native conformation of both polypeptides is changed into less ordered, metastable intermediates that are stabilised by formation of the more stable fibrils. In Aβ, the Glu at position 11 was found to be responsible for the conformational change at pH 4.6. Metal ions, including copper and zinc, could also induce conformational changes of Aβ at neutral pH. The acid modified Aβ conformer exhibited protease K resistance, preferential internalisation and accumulation in the human glial cells. In N-terminally truncated PrP90-231, spanning PrP residues 94-112 and the central region 146-154 incorporating Glu152 was identified as a significant participant for the conformational changes in acidic pH. In stefin B, reducing the pH to pH 3.3 results in another intermediate of the molten-globule type which also leads to amyloid fibril formation. Multiple sequence alignment revealed distinct similarities of Ab (1-42) peptide, stefin B (13 to 61 residues) and prion fragment (90 to 144 residues).
Keywords: amyloid b protein, prion protein, stefin b, molten-globule states, ph, elisa
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