Engineering a β-Sheet Protein toward the Folding Speed Limit

Publisher Website
Google Scholar
Abstract
Recent experimental studies have shown that α-helical proteins can approach the folding “speed limit”, where folding switches from an activated to a downhill process in free energy. β-sheet proteins are generally thought to fold more slowly than helix bundles. However, based on studies of hairpins, folding should still be able to approach the microsecond time scale. Here we demonstrate how the hPin1 WW domain, a triple-stranded β-sheet protein with a sharp thermodynamic melting transition, can be engineered toward the folding “speed limit” without a significant loss in thermal denaturation cooperativity.