title: Toward a mechanism of prion misfolding and structural models of PrP(Sc): current knowledge and future directions.
abstract: Despite extensive investigation, many features of prion protein misfolding remain enigmatic. Physicochemical variables known to influence misfolding are reviewed to help elucidate the mechanism of prionogenesis and identify salient features of PrP(Sc), the misfolded conformer of the prion protein. Prospective work on refinement of candidate PrP(Sc) models based on thermodynamic considerations will help to complete atomic-scale structural details missing from experimental studies and may explain the basis for the templating activity of PrP(Sc) in disease.
authors.affiliation: Brain Research Centre, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Will C
authors.initials: WC
authors.lastname: Guest
authors.forename: Steven S
authors.initials: SS
authors.lastname: Plotkin
authors.forename: Neil R
authors.initials: NR
authors.lastname: Cashman
mesh_terms: D000818:Animals; D006863:Hydrogen-Ion Concentration; D008055:Lipids / Q000737:chemistry; D018620:PrPSc Proteins / Q000737:chemistry*; D017096:Prion Diseases / Q000209:etiology / Q000378:metabolism*; D011328:Prions / Q000737:chemistry*; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D054712:Salinity
chemical_list: D008055:Lipids; D018620:PrPSc Proteins; D011328:Prions