Physicochemical and Structural Studies on Shaping of β-hairpin in Proteins as a First Stage of Amyloid Formation

The aggregation of proteins or their digested fragments through beta-sheet structures has a great significance because it leads to neurodegenerative diseases, which are a problem of the aging societies of the developed countries. Short peptides are typically used as models to study the formation of specific structures. However, while the formation of alpha-helical structure was investigated thoroughly, until recently, there have been much fewer studies on the formation of beta-structure. In this review, recent experimental and theoretical studies of beta-hairpin-forming peptides, both model alaninebased systems, and those based on the fragments of real proteins, are summarized with regard to the role of hydrophobic, local, and Coulombic interactions. It is demonstrated that the presence of charged residues can induce a bent structure not only owing to the formation of salt bridges if oppositely-charged residues present at the ends of a sequence but also through shielding the hydrophobic interior by like-charged residues at the end of the sequence.