( etely change its ability to infect a pr...)Fibril Shape Is The Basis Of Prion Strains And Cross-species Prion Infection

In a study published last year in the journal Molecular Cell, Surewuicz and colleagues also demonstrated that a "preseeding" process between animals with different prion amino acid sequences could overcome species barriers. For instance, mouse prion fibrils normally infect humans but not hamsters. But when mouse prions were brought into contact with hamster prion amyloid fibrils, a new strain of mouse fibrils emerged with the ability to infect hamsters but not humans. The new mouse strain had the same amino acid sequence as the original mouse strain but completely different infectious capabilities.

With the help of atomic-level microscopic observation of prions in humans, mice, and hamsters, Jones and Surewicz discovered that it is the specific shape of the amyloid fibrils, and not the amino acid sequences, that may allow prions from one species to infect another.

In a second Cell study, Jonathan Weissman and colleagues at the University of California, San Francisco came to the same conclusion in their experiments with yeast. They too discovered that the particular shape of a prion amyloid fibril was the determining factor in whether one species of yeast could infect another yeast species.

Just as in the case with the preseeded mice fibrils, a particular fibril shape in Saccharomyces cerevisiae yeast allowed prion transmission to Candida albicans yeast. The transmission event led to a new strain of Candida prion fibrils that could in turn infect Saccharomyces.

Although fibril shape appears to be the deciding infective factor, amino acid sequence is still important because it defines a set of possible preferred fibril shapes that prions can adopt, Weissman says. Species with similar amino acids sequences share an overlapping set of shapes, which helps explain why species with shared sequences have the ability to infect each othe
'"/>

Source:Cell Press