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Unweaving amyloid fibers to solve prion puzzles

cture, he instead used a combination of low resolution tools to analyze varieties of prion strains and piece together the puzzle of how amyloids form.

"We now have an overall picture of how prions join together to form the amyloid's molecular structure," says Lindquist, who also is a professor of biology at MIT.

Prions are in the business of converting other prion molecules to join their ranks. And as they join together, they can create an amyloid fiber. To understand the nature of this fiber, it's necessary to understand how the prions that comprise it attach to each other. Krishnan was able to identify the precise segment at which the prions interact--something that no one had done before him with a real prion.

To do this, Krishnan took a variety of yeast prion strains and modified them in such a way that if particular designated regions came into contact with each other, they would emit a fluorescent signal, allowing him to map the pattern by which the different strains of prions interacted with each other.

He found that each prion molecule had only two points at which they connected to other prion molecules. One point he called the "head," the other the "tail." The head of one prion would only interact with the head of another prion, and likewise with tails. Remarkably, the same prion from the same yeast species could sometimes fold differently, and this fold would form its own cascade of interactions. In this altered form, the prion molecules interact in slightly different places, presenting different surfaces to promote the conversion of other prion molecules.

Lindquist believes that the techniques used in this study will ultimately prove useful for studying prion strains found in mammals like mice, cows, and ultimately humans.

"This gives us insight as to why some prions can't cross the species barrier while others can--as they have with mad cows and humans.," says Lindquist. That gap has also been observed betw
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Source:Whitehead Institute for Biomedical Research


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