title: Designed Trpzip-3 β-Hairpin Inhibits Amyloid Formation in Two Different Amyloid Systems.
abstract: The trpzip peptides are small, monomeric, and extremely stable β-hairpins that have become valuable tools for studying protein folding. Here, we show that trpzip-3 inhibits aggregation in two very different amyloid systems: transthyretin and Aβ(1-42). Interestingly, Trp → Leu mutations renders the peptide ineffective against transthyretin, but Aβ inhibition remains. Computational docking was used to predict the interactions between trpzip-3 and transthyretin, suggesting that inhibition occurs via binding to the outer region of the thyroxine-binding site, which is supported by dye displacement experiments.
authors.affiliation: Department of Bioengineering, University of Washington , Seattle, Washington 98195, United States.
authors.forename: Gene
authors.initials: G
authors.lastname: Hopping
authors.affiliation: Department of Bioengineering, University of Washington , Seattle, Washington 98195, United States.
authors.forename: Jackson
authors.initials: J
authors.lastname: Kellock
authors.affiliation: Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Hamilton, Montana 59840, United States.
authors.forename: Byron
authors.initials: B
authors.lastname: Caughey
authors.affiliation: Department of Bioengineering, University of Washington , Seattle, Washington 98195, United States.
authors.forename: Valerie
authors.initials: V
authors.lastname: Daggett
keywords: ANS fluorescence; Alzheimer’s disease; Trpzip; computational docking; transthyretin