title: Cryptic peptides of the kringle domains preferentially bind to disease-associated prion protein.
abstract: Prion diseases are a group of fatal neurodegenerative disorders characterized by the accumulation of a misfolded form (PrP(Sc)) of the cellular prion protein (PrP(C)) in the brains of affected individuals. The conversion of PrP(C) to PrP(Sc) is thought to involve a change in protein conformation from a normal, primarily alpha-helical structure into a beta-sheet conformer. Few proteins have been identified that differentially interact with the two forms of PrP. It has been reported that plasminogen binds to PrP(Sc) from a variety of prion phenotypes. We have examined potential motifs within the kringle region that may be responsible for binding to PrP. We synthesized 12-15-mer peptides that contain small, repetitive stretches of amino acid residues found within the kringle domains of plasminogen. These synthetic peptides were found to capture PrP(Sc) from the brain homogenates of bovine spongiform encephalopathy affected cattle, chronic wasting disease affected elk, experimental scrapie of hamsters and that of subjects affected by Creutzfeldt-Jakob disease, without binding to PrP(C) in unaffected controls. Therefore, we have identified critical peptide motifs that may be important for protein-protein interactions in prion disease pathogenesis. The ability of these synthetic peptides to bind preferentially to PrP(Sc) suggests a potential application in the diagnosis of prion diseases.
authors.affiliation: Department of Pathology and National Prion Disease Pathology Surveillance Center, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Kristen
authors.initials: K
authors.lastname: Hatcher
authors.forename: Jian
authors.initials: J
authors.lastname: Zheng
authors.forename: Shu G
authors.initials: SG
authors.lastname: Chen
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002417:Cattle; D007562:Creutzfeldt-Jakob Syndrome / Q000378:metabolism / Q000473:pathology; D003670:Deer; D006801:Humans; D007118:Immunoassay / Q000379:methods; D018082:Kringles / Q000502:physiology*; D009154:Mutation; D010446:Peptide Fragments / Q000737:chemistry* / Q000494:pharmacology; D010958:Plasminogen / Q000737:chemistry; D017096:Prion Diseases / Q000473:pathology*; D011328:Prions / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D011487:Protein Conformation / Q000187:drug effects; D034081:Wasting Disease, Chronic / Q000378:metabolism / Q000473:pathology
chemical_list: D010446:Peptide Fragments; D011328:Prions; D010958:Plasminogen