Abstract
Amyloid beta (Aβ) protein is the key component of amyloid plaques in Alzheimers disease 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 4.6, the native conformation of both polypeptides are changed into less ordered metastable intermediates that are stabilized 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 internalization and accumulation in the human glial cells. In stefin B, reducing the pH to pH 3.3 results in another intermediate of the moltenglobule type which also leads to amyloid fibril formation. Multiple sequence alignment revealed distinct similarities of Aβ (1-42) peptide, stefin B (13 to 61 residues) and prion fragment (90 to 144 residues).
Keywords: Amyloid, metal ions, protease resistance, stefin B, cystatins, molten globule, amyloidfibrillogenesis
Current Medicinal Chemistry
Title: Conformational Changes Preceding Amyloid-fibril Formation of Amyloid-beta and Stefin B; Parallels in pH Dependence
Volume: 9 Issue: 19
Author(s): Yoichi Matsunaga, Eva Zerovnik, Tatsuo Yamada and Vito Turk
Affiliation:
Keywords: Amyloid, metal ions, protease resistance, stefin B, cystatins, molten globule, amyloidfibrillogenesis
Abstract: Amyloid beta (Aβ) protein is the key component of amyloid plaques in Alzheimers disease 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 4.6, the native conformation of both polypeptides are changed into less ordered metastable intermediates that are stabilized 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 internalization and accumulation in the human glial cells. In stefin B, reducing the pH to pH 3.3 results in another intermediate of the moltenglobule type which also leads to amyloid fibril formation. Multiple sequence alignment revealed distinct similarities of Aβ (1-42) peptide, stefin B (13 to 61 residues) and prion fragment (90 to 144 residues).
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Matsunaga Yoichi, Zerovnik Eva, Yamada Tatsuo and Turk Vito, Conformational Changes Preceding Amyloid-fibril Formation of Amyloid-beta and Stefin B; Parallels in pH Dependence, Current Medicinal Chemistry 2002; 9 (19) . https://dx.doi.org/10.2174/0929867023369097
DOI https://dx.doi.org/10.2174/0929867023369097 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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