title: Lipopolysaccharide induced conversion of recombinant prion protein.
abstract: The conformational conversion of the cellular prion protein (PrP(C)) to the β-rich infectious isoform PrP(Sc) is considered a critical and central feature in prion pathology. Although PrP(Sc) is the critical component of the infectious agent, as proposed in the "protein-only" prion hypothesis, cellular components have been identified as important cofactors in triggering and enhancing the conversion of PrP(C) to proteinase K resistant PrP(Sc). A number of in vitro systems using various chemical and/or physical agents such as guanidine hydrochloride, urea, SDS, high temperature, and low pH, have been developed that cause PrP(C) conversion, their amplification, and amyloid fibril formation often under non-physiological conditions. In our ongoing efforts to look for endogenous and exogenous chemical mediators that might initiate, influence, or result in the natural conversion of PrP(C) to PrP(Sc), we discovered that lipopolysaccharide (LPS), a component of gram-negative bacterial membranes interacts with recombinant prion proteins and induces conversion to an isoform richer in β sheet at near physiological conditions as long as the LPS concentration remains above the critical micelle concentration (CMC). More significant was the LPS mediated conversion that was observed even at sub-molar ratios of LPS to recombinant ShPrP (90-232).
authors.affiliation: Department of Biological Sciences; University of Alberta; Edmonton, AB Canada.
authors.forename: Fozia
authors.initials: F
authors.lastname: Saleem
authors.affiliation: Department of Computing Science; University of Alberta; Edmonton, AB Canada.
authors.forename: Trent C
authors.initials: TC
authors.lastname: Bjorndahl
authors.affiliation: Department of Computing Science; University of Alberta; Edmonton, AB Canada; National Institute for Nanotechnology; Edmonton, AB Canada.
authors.forename: Carol L
authors.initials: CL
authors.lastname: Ladner
authors.affiliation: Department of Computing Science; University of Alberta; Edmonton, AB Canada.
authors.forename: Rolando
authors.initials: R
authors.lastname: Perez-Pineiro
authors.affiliation: Department of Agricultural, Food and Nutritional Science; University of Alberta; Edmonton, AB Canada.
authors.forename: Burim N
authors.initials: BN
authors.lastname: Ametaj
authors.affiliation: Department of Biological Sciences; University of Alberta; Edmonton, AB Canada; Department of Computing Science; University of Alberta; Edmonton, AB Canada; National Institute for Nanotechnology; Edmonton, AB Canada.
authors.forename: David S
authors.initials: DS
authors.lastname: Wishart
mesh_terms: D006358:Hot Temperature; D006863:Hydrogen-Ion Concentration; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008854:Microscopy, Electron; D011328:Prions / Q000737:chemistry / Q000187:drug effects*; D011489:Protein Denaturation; D011994:Recombinant Proteins / Q000737:chemistry / Q000187:drug effects
chemical_list: D008070:Lipopolysaccharides; D011328:Prions; D011994:Recombinant Proteins
keywords: beta oligomer; fibril; lipopolysaccharide; prion protein; protein misfolding