Design of Functional Globular β-Sheet Miniproteins

4Citations
Citations of this article
10Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

The design of discrete β-sheet peptides is far less advanced than e. g. the design of α-helical peptides. The reputation of β-sheet peptides as being poorly soluble and aggregation-prone often hinders active design efforts. Here, we show that this reputation is unfounded. We demonstrate this by looking at the β-hairpin and WW domain. Their structure and folding have been extensively studied and they have long served as model systems to investigate protein folding and folding kinetics. The resulting fundamental understanding has led to the development of hyperstable β-sheet scaffolds that fold at temperatures of 100 °C or high concentrations of denaturants. These have been used to design functional miniproteins with protein or nucleic acid binding properties, in some cases with such success that medical applications are conceivable. The β-sheet scaffolds are not always completely rigid, but can be specifically designed to respond to changes in pH, redox potential or presence of metal ions. Some engineered β-sheet peptides also exhibit catalytic properties, although not comparable to those of natural proteins. Previous reviews have focused on the design of stably folded and non-aggregating β-sheet sequences. In our review, we now also address design strategies to obtain functional miniproteins from β-sheet folding motifs.

Cite

CITATION STYLE

APA

Pham, T. L., & Thomas, F. (2024, April 2). Design of Functional Globular β-Sheet Miniproteins. ChemBioChem. John Wiley and Sons Inc. https://doi.org/10.1002/cbic.202300745

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free