Affiliations: [a] Department of Pathology and National Prion Disease Pathology Surveillance Center, Case Western Reserve University, Cleveland, OH, USA | [b] Ortho-Clinical Diagnostics, Raritan, NJ, USA
Correspondence:
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Corresponding author: Shu G. Chen, Ph.D., Department of Pathology, Case Western Reserve University, 2103 Cornell Road, Cleveland, Ohio 44106, USA. Tel.: +1 216 368 8925; Fax: +1 216 368 2546; E-mail: [email protected].
Abstract: Prion diseases are a group of fatal neurodegenerative disorders characterized by the accumulation of a misfolded form (PrPSc) of the cellular prion protein (PrPC) in the brains of affected individuals. The conversion of PrPC to PrPSc is thought to involve a change in protein conformation from a normal, primarily α-helical structure into a β-sheet conformer. Few proteins have been identified that differentially interact with the two forms of PrP. It has been reported that plasminogen binds to PrPSc 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 PrPSc 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 PrPC 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 PrPSc suggests a potential application in the diagnosis of prion diseases.
