"For years we've wondered why evolution has preserved this protein, what positive role it could possibly be playing," says Whitehead Member Susan Lindquist. Along with Whitehead Member Harvey Lodish, Lindquist is a coauthor on the paper which will published online in Proceedings of the National Academy of Sciences during the week of January 30. "With these findings, we have our first answer," she says.
For over ten years, researchers have known that a protein called PrP causes mad cow disease and its human equivalent, Creutzfeld-Jakob disease. PrP is a prion, a class of proteins that has the unusual ability to recruit other proteins to change their shape (PrP is shorthand for "prion protein."). This is significant, because a protein's form determines its function. When a prion changes shape, or "misfolds," it creates a cascade where neighboring proteins all assume that particular conformation. In some organisms, such as yeast cells, this process can be harmless, even beneficial. But in mammals, it can lead to the fatal brain lesions that characterize diseases such as Creutzfeld-Jakob.
Curiously, however, PrP can be found throughout healthy human bodies, particularly in the brain where it's highly abundant. In fact, it's found in many mammalian species, and only on the rarest occasions does it result in disease. Clearly, scientists have reasoned, such a widely conserved protein also must play a positive role.
In 1993, scientists created a line of mice in which the gene that codes for PrP was knocked out, preventing the mice from expressing the prion in any tissues. Surprisingly, the mice appeared
Contact: David Cameron
Whitehead Institute for Biomedical Research