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The role of proline‐containing peptide triads in β‐sheet formation: A kinetic study
Author(s) -
Takor Gaius A.,
Higashiya Seiichiro,
Sikirzhytski Vitali K.,
Seeley Jason P.,
Lednev Igor K.,
Welch John T.
Publication year - 2015
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.22622
Subject(s) - proline , chemistry , folding (dsp implementation) , circular dichroism , peptide , crystallography , protein folding , amino acid , biochemistry , electrical engineering , engineering
The design of biomimetic materials through molecular self‐assembly is a growing area of modern nanotechnology. With problems of protein folding, self‐assembly, and sequence–structure relationships as essential in nanotechnology as in biology, the effect of the nucleation of β‐hairpin formation by proline on the folding process has been investigated in model studies. Previously such studies were limited to investigations of the influence of proline on the formation of turns in short peptide sequences. The effect of proline‐based triads on the folding of an 11‐kDa amyloidogenic peptide GH 6 [(GA) 3 GY(GA) 3 GE] 8 GAH 6 ( YE8 ) was investigated by selective substitution of the proline‐substituted triads at the γ‐turn sites. The folding and fibrillation of the singly proline‐substituted polypeptides, e.g., GH6[(GA)3GY(GA)3GE]7(GA)3GY(GA)3PDGAH6 ( 8PD ), and doubly proline‐substituted polypeptides, e.g., GH6[(GA)3GY(GA)3GE]3(GA)3GY(GA)3PD[(GA)3GY(GA)3GE]3(GA)3GY(GA)3PDGAH6 ( 4,8PD ), were directly monitored by circular dichroism and deep UV resonance Raman and fluorescence spectroscopies. These findings were used to identify the essential folding domains, i.e., the minimum number of β‐strands necessary for stable folding. These experimental findings may be especially useful in the design and construction of peptidic materials for a wide range of applications as well as in understanding the mechanisms of folding critical to fibril formation. © 2015 Wiley Periodicals, Inc. Biopolymers 103: 339–350, 2015.