title: A cluster of familial Creutzfeldt-Jakob disease mutations recapitulate conserved residues in Doppel: a case of molecular mimicry?
abstract: Intrachromosomal deletions linking Dpl expression to the PrP promoter produce cerebellar degeneration that can be abrogated by the introduction of wild-type PrP transgenes. Since Dpl-like truncated forms of PrP are neuropathogenic in mice and likewise counterbalanced by expression of PrP(C) we asked whether naturally occurring mutant forms of human PrP have Dpl-like attributes. Five PRNP missense mutations causing familial Creutzfeldt-Jakob disease (F-CJD) map to a helical region found in both PrP(C) and Dpl and result in amino acids identical to conserved residues in Dpl. These F-CJD alleles may cause mutant PrP to become a weak mimetic of Dpl structure and/or function.
authors.affiliation: Centre for Research in Neurodegenerative Diseases, University of Toronto, Tanz Neuroscience Building, 6 Queen's Park Crescent West, Toronto, ON, Canada M5S 3H2.
authors.forename: Peter
authors.initials: P
authors.lastname: Mastrangelo
authors.forename: Louise
authors.initials: L
authors.lastname: Serpell
authors.forename: Tim
authors.initials: T
authors.lastname: Dafforn
authors.forename: Arthur
authors.initials: A
authors.lastname: Lesk
authors.forename: Paul
authors.initials: P
authors.lastname: Fraser
authors.forename: David
authors.initials: D
authors.lastname: Westaway
mesh_terms: D000595:Amino Acid Sequence; D000682:Amyloid / Q000235:genetics*; D000818:Animals; D002417:Cattle; D017124:Conserved Sequence; D007562:Creutzfeldt-Jakob Syndrome / Q000235:genetics*; D019143:Evolution, Molecular; D058851:GPI-Linked Proteins; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D000072002:Prion Proteins; D011328:Prions / Q000737:chemistry / Q000235:genetics*; D011498:Protein Precursors / Q000235:genetics*; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D012756:Sheep
chemical_list: D000682:Amyloid; D058851:GPI-Linked Proteins; C501125:PRND protein, human; C512656:PRNP protein, human; D000072002:Prion Proteins; D011328:Prions; C122036:Prnd protein, mouse; C512657:Prnp protein, mouse; D011498:Protein Precursors