Charge distribution and amyloid fibril formation: insights from genetically engineered model systems.
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 beta-sheet forming polypeptides were designed with identical beta-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 beta-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.
Topilina
Natalya I
NI
Department of Chemistry, University at Albany, State University of New York, Albany, New York 12222, USA.
Sikirzhytsky
Vitali
V
Higashiya
Seiichiro
S
Ermolenkov
Vladimir V
VV
Lednev
Igor K
IK
Welch
John T
JT
D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry* / Q000235:genetics*; D010455:Peptides; D015202:Protein Engineering; D017510:Protein Folding; D012995:Solubility; D055672:Static Electricity
D000682:Amyloid; D010455:Peptides