title: De novo design of synthetic prion domains.
abstract: Prions are important disease agents and epigenetic regulatory elements. Prion formation involves the structural conversion of proteins from a soluble form into an insoluble amyloid form. In many cases, this structural conversion is driven by a glutamine/asparagine (Q/N)-rich prion-forming domain. However, our understanding of the sequence requirements for prion formation and propagation by Q/N-rich domains has been insufficient for accurate prion propensity prediction or prion domain design. By focusing exclusively on amino acid composition, we have developed a prion aggregation prediction algorithm (PAPA), specifically designed to predict prion propensity of Q/N-rich proteins. Here, we show not only that this algorithm is far more effective than traditional amyloid prediction algorithms at predicting prion propensity of Q/N-rich proteins, but remarkably, also that PAPA is capable of rationally designing protein domains that function as prions in vivo.
authors.affiliation: Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO 80523, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Toombs
authors.forename: Michelina
authors.initials: M
authors.lastname: Petri
authors.forename: Kacy R
authors.initials: KR
authors.lastname: Paul
authors.forename: Grace Y
authors.initials: GY
authors.lastname: Kan
authors.forename: Asa
authors.initials: A
authors.lastname: Ben-Hur
authors.forename: Eric D
authors.initials: ED
authors.lastname: Ross
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D008969:Molecular Sequence Data; D011328:Prions / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid; D012995:Solubility
chemical_list: D011328:Prions