Charge Distribution and Amyloid Fibril Formation: Insights from Genetically Engineered Model Systems

详细信息    查看全文

• 作者：Natalya I. Topilina ; Vitali Sikirzhytsky ; Seiichiro Higashiya ; Vladimir V. Ermolenkov ; Igor K. Lednev ; John T. Welch
• 刊名：Biomacromolecules
• 出版年：2010
• 出版时间：July 12, 2010
• 年：2010
• 卷：11
• 期：7
• 页码：1721-1726
• 全文大小：254K
• 年卷期：v.11,no.7(July 12, 2010)
• ISSN：1526-4602

文摘

The influence of electrostatic interactions on protein amyloidogenesis has been investigated using de novo designed repetitive polypeptides YEHK21 [GH₆[(GA)₃GY(GA)₃GE(GA)₃GY(GA)₃GE]₂₁GAH₆] and YE8 [GH₆[(GA)₃GY(GA)₃GE]₈GAH₆]. The β-sheet forming polypeptides were designed with identical β-strands but with variable substitution at the turns that enable precise location of charged residues (Topilina et al. Biopolymers 2007, 86 (4), 261−264; Topilina et al. Biopolymers 2010, submitted for publication; Topilina et al. Biomacromolecules 2006, 7 (4), 1104−11). Solubility, folding, and aggregation of YEHK21 and YE8 were shown to be controlled by charge distribution. Under those conditions favoring the development of charge, YEHK21 and YE8 have significant propensities to form intermolecular β-sheet assemblies illustrating the potential of charged polypeptide chains to form ordered amyloid aggregates even in the absence of additional environmental factors such as the presence of polyelectrolytes, salts, and so on.