Oligomerization of yeast prion Sup35NM

The yeast Sup35NM domain propagates as a prion in mammalian cells.

Prions are infectious, self-propagating amyloid-like protein aggregates of mammals and fungi. We have studied aggregation propensities of a yeast prion domain in cell culture to gain insights into general mechanisms of prion replication in mammalian cells. Here, we report the artificial transmission of a yeast prion across a phylogenetic kingdom. HA epitope-tagged yeast Sup35p prion domain NM w...

Assembly of the yeast prion

Direct Observation of Oligomerization by Single Molecule Fluorescence Reveals a Multistep Aggregation Mechanism for the Yeast Prion Protein Ure2

The self-assembly of polypeptides into amyloid structures is associated with a range of increasingly prevalent neurodegenerative diseases as well as with a select set of functional processes in biology. The phenomenon of self-assembly results in species with dramatically different sizes, from small oligomers to large fibrils; however, the kinetic relationship between these species is challengin...

Modelling prion dynamics in yeast

The word prion was coined by Nobel laureate Stanley Prusiner to describe the infectious agent in a group of fatal neurodegenerative diseases that includes scrapie in sheep, bovine spongiform encephalopathy (BSE) in cattle and variant Creutzfeldt-Jakob disease (vCJD) in humans. The infectious agent is a misfolded form of the protein, PrP, denoted PrPSc, which forms polymers that grow by recruiti...

Copper-induced structural conversion templates prion protein oligomerization and neurotoxicity

Prion protein (PrP) misfolding and oligomerization are key pathogenic events in prion disease. Copper exposure has been linked to prion pathogenesis; however, its mechanistic basis is unknown. We resolve, with single-molecule precision, the molecular mechanism of Cu(2+)-induced misfolding of PrP under physiological conditions. We also demonstrate that misfolded PrPs serve as seeds for templated...