Prion-forming proteins normally exist as normal cellular components. But they possess the innate ability to alter their three-dimensional structure, which changes their function and makes them almost impossible to destroy. Prions grow by inducing normal proteins to alter their shape and adhere to an initial aggregate “seed.” These growing masses are then thought to divide with the help of “chaperones,” cellular proteins that aid in protein folding and transport, resulting in smaller prion particles called propagons. The propagons are then distributed to both mother and daughter cells during division, thereby infecting the next generation of cells.

Lev Osherovich and colleagues confirmed what others have seen, namely that an area rich in glutamine and asparagine was responsible for the aggregation and growth of prions-acting like a patch of Velcro that locks the misshapen proteins together. They went on to find that a short stretch of peptide repeats was required for the inheritance of prions – the proper division of prion masses and subsequent distribution of propagons during cell division. The authors suggest that oligopeptide repeats function as a secure binding location for chaperone proteins, which are necessary for heritability, and thus infectiousness, of prions. These results help explain why stable inheritance of prions is rare; while many proteins have stretches of amino acids similar to the aggregation sequence, few also contain sequences that permit inheritance. Osherovich and colleagues were able to create an artificial prion by fusing the oligopeptide repeats to an expanded polyglutamine tract.

By creating artificial hybrid prions, Osherovich and colleagues showed that the two discrete elements of prion-forming domains are portable and work together regardless of their origins. The authors suggest that other artificial prions could be used as a model system to study different types of aggregation sequences, such as those found in the human prion protein responsible for Creutzfeldt-Jakob’s disease or the misshapen plaques of proteins that contribute to Alzheimer’s disease.