Thermostable WW-Domain Scaffold to Design Functional β-Sheet Miniproteins

There has been a recent surge in the design of miniproteins for medicinal chemistry, biomaterial design, or synthetic biology. In particular, there is an interest in peptide scaffolds that fold reliably, predictably, and with solid stability. In this article, we present the design of a highly thermostable WW domain, a three-stranded β-sheet motif, with a superior melting temperature of about 90 °C to serve as a core scaffold onto which receptor-like properties can be grafted. We have …