Short primary peptide structure drives the nucleation and self-perpetuation of prions, report Peter Tessier and Susan Lindquist (HHMI, Cambridge, MA).
Prions self-perpetuate by binding their normal protein counterparts and inducing them to fold into the same abnormal conformation. Previous studies of a yeast prion called Sup35 identified a broad region of the protein that is responsible for initiating this self-perpetuation. Part of the region has unusually low sequence complexity, suggesting that its overall structure, rather than its particular amino acid sequence, might be responsible for prion proliferation. Indeed many protein domains that promote folding are themselves organized into complex tertiary structures.
Single amino acid substitutions of the low-complexity region, however, can increase or decrease Sup35's prion-perpetuating ability. To see whether particular peptide elements might therefore be responsible, Tessier and Lindquist arrayed overlapping peptides from the broad suspect region of Sup35 onto glass slides. Only a very small set of overlapping peptides could bind and nucleate prions. And the longer the incubation continued, the more the Sup35 prion amyloids grew at these particular peptide spots.
Exactly how binding promotes conformational change is unclear. But whatever the mechanism, it does not appear to be unique to Sup35. Another distantly related yeast prion possessed a similarly short cluster of unrelated sequences capable of nucleating prions. Determining whether such sequences, which the authors call recognition elements, promote amyloid production in mammalian prions is the next step. 
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