Reconstructing prions: fibril assembly from simple yeast to complex mammals.

With the epizootics of bovine spongiform encephalopathy (BSE) in North American cattle, BSE infections in goats, new forms of human Creutzfeldt-Jakob disease (CJD) and the spread of chronic wasting disease in North American deer and elk, one wonders whether we are gaining control over the transmissible spongiform encephalopathies (TSEs). Although many basic scientific questions in the prion field remain hotly debated and unresolved [1], including the function of the cellular prion protein (PrP), light has been shed on a diverse array of topics, and discussions at the latest TSE meeting ranged broadly from yeast prion fibril assembly to mammalian prion neurotoxicity to future TSE therapies. Prion diseases are protein misfolding disorders which cause degeneration of the central nervous system (CNS) and ultimately death. The unique and surprising feature is that prion diseases are infectious. Yeast prions are derived from proteins differing from the mammalian PrP but are also infectious, self propagating proteins which typically can convert into an aggregated, amyloidogenic form having high beta sheet content. The simple yeast organism has served as a valuable model for understanding aspects of prion biology, such as prion fibril assembly.