title: Human cellular prion protein interacts directly with clusterin protein.
abstract: Prion protein is a glycosyl-phosphatidyl-inositol anchored glycoprotein localized on the surface and within a variety of cells. Its conformation change is thought to be essential for the proliferation of prion neurodegenerative diseases. Using the yeast two-hybrid assay we identified an interaction between prion protein and clusterin, a chaperone glycoprotein. This interaction was confirmed in a mammalian system by in vivo co-immunoprecipitation and in vitro by circular dichroism analysis. Through deletion mapping analysis we demonstrated that the alpha subunit, but not the beta subunit, of clusterin binds to prion and that the C-terminal 62 amino acid segment of the putative alpha helix region of clusterin is essential for the binding interaction. The full prion protein as well as the N-terminal section (aa 23-95) and C-terminal (aa 96-231) were shown to interact with clusterin. These findings provide new insights into the molecular mechanisms of interaction between prion and clusterin protein and contribute to the understanding of prion protein's physiological function.
authors.affiliation: Division of Hematology, Office of Blood Research and Review, Center for Biologics Evaluation and Research, United States Food and Drug Administration, Bethesda, MD, USA.
authors.forename: Fei
authors.initials: F
authors.lastname: Xu
authors.forename: Elena
authors.initials: E
authors.lastname: Karnaukhova
authors.forename: Jaroslav G
authors.initials: JG
authors.lastname: Vostal
mesh_terms: D000818:Animals; D002460:Cell Line; D051152:Clusterin / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D018621:PrPC Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D020798:Two-Hybrid System Techniques
chemical_list: D051152:Clusterin; D008024:Ligands; D018832:Molecular Chaperones; D018621:PrPC Proteins; D021122:Protein Subunits