title: The role of proline-containing peptide triads in β-sheet formation: A kinetic study.
abstract: 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 GH6[(GA)3GY(GA)3GE]8 GAH6 (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)3PD-GAH6 (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)3PD-GAH6 (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.
authors: Department of Chemistry, University at Albany, State University of New York, Albany, NY, 12222.
authors: Gaius A
authors: GA
authors: Takor
authors: Seiichiro
authors: S
authors: Higashiya
authors: Vitali K
authors: VK
authors: Sikirzhytski
authors: Jason P
authors: JP
authors: Seeley
authors: Igor K
authors: IK
authors: Lednev
authors: John T
authors: JT
authors: Welch
mesh_terms: D000595:Amino Acid Sequence; D002942:Circular Dichroism; D007700:Kinetics; D010455:Peptides / Q000737:chemistry*; D011392:Proline / Q000737:chemistry*; D017510:Protein Folding; D017433:Protein Structure, Secondary
chemical_list: D010455:Peptides; D011392:Proline
keywords: proline-based triads; synthetic amyloidogenic protein; β-sheet; β-sheet nucleation