Clues to how prions cross the species barrier

A hybrid prion, created by fusing together prions from two distantly related yeast species, can adopt two distinct shapes and infect both yeast species.

By | March 8, 2001

Yeast cells manufacture a protein called Sup35, which displays prion-like behaviour: it forms aggregates and converts its normal counterpart to the prion version. Previous work by Peter Chien and Jonathan Weissman of the University of California, San Francisco, showed that a species barrier prevents the prion version of Sup35 in one yeast species from converting Sup35 of a different yeast species into the prion version, and vice versa (Cell 2000, 100:277-288).

In a study published in 8 March Nature, Chien and Weissman engineered a chimaeric prion that combined Sup35 segments from two yeast species — Saccharomyces cerevisiae and Candida albicans. When introduced into each species of yeast, the chimaera could adopt the shape of the prion specific for that species (Nature 2001, 410:223-227).

The results suggest that a single protein — in this case Sup35 — can adopt many prion conformations, some of which could cause infection across species barriers. This phenomenon may be a key to understanding how prions derived from cows infected with bovine spongiform encephalopathy (BSE) can cross the species barrier and infect humans. Weissman says, "the shape of a prion may evolve as it passes from host to host. If this is the case, then the processing of animal parts for subsequent use as feed for other animals may actually have selected for animal prions with conformations that are especially virulent."

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