Monday, November 6, 2006

Synthetic prions

carbonbasedunit writes "In the 20 years since Prusiner popularized Griffith’s suggestion that infectious protein causes Creutzfeld-Jacob disease, the "protein-only" hypothesis has matured from radical to conventional. The hardy doubters not cowed by the 1997 Nobel prize still argued that the infectious agent in brain preparations had not been proven to be protein but could instead be contaminating nucleic acids (review).
Now Legname et al. show that when polymerized into amyloid fibrils and injected into the brains of mice, recombinant mouse prion protein produced in bacteria induces neurologic disease. They previously showed that disease was accelerated in disease-prone mice treated with a synthetic 55 amino acid peptide matching a fragment of a mutant (P101L) human prion that causes spontaneous disease in younger adults. Here, they produced fibrils from a recombinant, truncated mouse prion in mice that do not develop the disease spontaneously. Rather than having fortuitously refolded in vitro a natural prion form, the authors instead suggest based on histology that a novel strain of prion was created. Is there a potential Pandora’s box of prions?
PubMed Synthetic mammalian prions. Legname G, Baskakov IV, Nguyen HO, Riesner D, Cohen FE, DeArmond SJ, Prusiner SB. Science. 2004 Jul 30;305(5684):673-6.

1 comment:

Anonymous said...

Do it yourself?
Alicon [] sells "pure" prion proteins (PrP) folded in conformations that are largely alpha-helical or contain significant beta-sheet. They term the first "PrP-pure" and the second "PrP-beta" or scrapie (PrPSc). They are analyzed by NMR.
Their recombinant prion proteins are expressed in bacteria "and purified by high-affinity column refolding". They're initially His-tagged so the affinity column makes sense but the refolding would sound mysterious if they hadn't provided a handy reference (Zahn et al. 1997 [] "Human prion proteins expressed in Escherichia coli and purified by high-affinity column refolding")!