A hypothesis describing a potential link between molecular structure and TSE strains.
In considering a protein-only model for prion pathogenesis in TSEs, one key challenge is to explain the existence of strains. These have traditionally been characterised by neuropathology and incubation times and more recently through biochemical analysis of prion protein (PrP), which shows differences in protease-resistant fragment size and glycoform ratios. It is now suggested that PrP possesses two faces which on the basis of conservation and non-polar nature could each (physiologically) interact either with membrane or with neighbouring protein. This model leads to the construction of two clearly different membrane-attached PrP orientations, with consequences for protease resistance and glycoform incorporation that qualitatively match to experiment.
Warwicker
J
J
Institute of Food Research, Reading Laboratory, United Kingdom.
D000818:Animals; D019281:Dimerization; D010450:Endopeptidases; D006868:Hydrolysis; D009682:Magnetic Resonance Spectroscopy; D008565:Membrane Proteins / Q000737:chemistry; D051379:Mice; D008958:Models, Molecular; D008970:Molecular Weight; D010446:Peptide Fragments / Q000737:chemistry; D010641:Phenotype; D017096:Prion Diseases / Q000209:etiology* / Q000378:metabolism* / Q000635:transmission; D011328:Prions / Q000737:chemistry*; D017510:Protein Folding
D008565:Membrane Proteins; D010446:Peptide Fragments; D011328:Prions; D010450:Endopeptidases