A HYPOTHESIS DESCRIBING A POTENTIAL LINK BETWEEN MOLECULAR-STRUCTURE AND TSE STRAINS

In considering a protein-only model for prion pathogenesis in TSEs, on e key challenge is to explain the existence of strains. These have tra ditionally been characterised by neuropathology and incubation times a nd more recently through bic chemical analysis of prion protein (PrP), which shows differences in protease-resistant fragment size and glyco form ratios. It is now suggested that PrP possesses two faces which on the basis of conservation and non-polar nature could each (physiologi cally) interact; either with membrane or with neighbouring protein. Th is model leads to the construction of two clearly different membrane-a ttached PrP orientations, with consequences for protease resistance an d glycoform incorporation that qualitatively match to experiment. (C) 1997 Academic Press.