PROTEIN AGGREGATION DOMAINS FROM PRIONS AND METHODS OF USE THEREOF

摘要

Using the Sup35 prion proteins of two distantly related yeast species, it is established that prion replication is initiated by small elements of primary sequence, which can be identified using arrays of short peptides. Subtle differences in replication elements govern the formation of distinct aggregate conformations (prion strains) and also determine their species-specific seeding activities. A Sup35 chimera that promiscuously forms prions in more than one species does so by virtue of carrying the replication element of each species. Mutations or conditions that cause the chimera to assemble into distinct prion strains favor recognition of distinct replication elements. Therefore, subtle differences in small sequences that constitute prion replication elements encode important determinants of prion propagation and transmission. The protein aggregation domains, methods for identification thereof, and polypeptides and higher order aggregates including the protein interaction domains, as well as arrays including peptides derived from an aggregation-prone polypeptide are provided.