title: Identification of cellular proteins binding to the scrapie prion protein.
abstract: The scrapie prion protein (PrPSc) is an abnormal isoform of the cellular protein PrPc. PrPSc is found only in animals with scrapie or other prion diseases. The invariable association of PrPSc with infectivity suggests that PrPSc is a component of the infectious particle. In this study, we report the identification of two proteins from hamster brain of 45 and 110 kDa (denoted PrP ligands Pli 45 and Pli 110) which were able to bind to PrP 27-30, the protease-resistant core of PrPSc on ligand blots. Pli 45 and Pli 110 also bound PrPC. Both Pli's had isoelectric points of approximately 5. The dissociation rate constant of the Pli 45/PrP 27-30 complex was 3 x 10(-6) s-1. Amino acid and protein sequence analyses were performed on purified Pli 45. Both the composition and the sequence were almost identical with those predicted for mouse glial fibrillary acidic protein (GFAP). Furthermore, antibodies to Pli 45 reacted with recombinant GFAP. The identification of proteins which interact with the PrP isoforms in normal and diseased brain may provide new insights into the function of PrPC and into the molecular mechanisms underlying prion diseases.
authors.affiliation: Department of Neurology, University of California, San Francisco 94143.
authors.forename: B
authors.initials: B
authors.lastname: Oesch
authors.forename: D B
authors.initials: DB
authors.lastname: Teplow
authors.forename: N
authors.initials: N
authors.lastname: Stahl
authors.forename: D
authors.initials: D
authors.lastname: Serban
authors.forename: L E
authors.initials: LE
authors.lastname: Hood
authors.forename: S B
authors.initials: SB
authors.lastname: Prusiner
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000276:immunology; D001921:Brain / Q000378:metabolism*; D006224:Cricetinae; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D008969:Molecular Sequence Data; D018620:PrPSc Proteins; D011817:Rabbits; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: D000906:Antibodies; D005904:Glial Fibrillary Acidic Protein; D018620:PrPSc Proteins; D011994:Recombinant Proteins; D014764:Viral Proteins