title: Identification of PrP sequences essential for the interaction between the PrP polymers and Aβ peptide in a yeast-based assay.
abstract: Alzheimer disease is associated with the accumulation of oligomeric amyloid β peptide (Aβ), accompanied by synaptic dysfunction and neuronal death. Polymeric form of prion protein (PrP), PrP(Sc), is implicated in transmissible spongiform encephalopathies (TSEs). Recently, it was shown that the monomeric cellular form of PrP (PrP(C)), located on the neuron surface, binds Aβ oligomers (and possibly other β-rich conformers) via the PrP(23-27) and PrP(90-110) segments, acting as Aβ receptor. On the other hand, PrP(Sc) polymers efficiently bind to Aβ monomers and accelerate their oligomerization. To identify specific PrP sequences that are essential for the interaction between PrP polymers and Aβ peptide, we have co-expressed Aβ and PrP (or its shortened derivatives), fused to different fluorophores, in the yeast cell. Our data show that the 90-110 and 28-89 regions of PrP control the binding of proteinase-resistant PrP polymers to the Aβ peptide, whereas the 23-27 segment of PrP is dispensable for this interaction. This indicates that the set of PrP fragments involved in the interaction with Aβ depends on PrP conformational state.
authors.affiliation: St. Petersburg Branch of Vavilov Institute of Genetics (Russian Academy of Science); Universitetskaya nab. 7/9; St. Petersburg, Russia; Department of Genetics and Biotechnology; St. Petersburg State University; Universitetskaya nab. 7/9; St. Petersburg, Russia.
authors.forename: Aleksandr A
authors.initials: AA
authors.lastname: Rubel
authors.forename: Tatyana A
authors.initials: TA
authors.lastname: Ryzhova
authors.forename: Kirill S
authors.initials: KS
authors.lastname: Antonets
authors.forename: Yury O
authors.initials: YO
authors.lastname: Chernoff
authors.forename: Alexey
authors.initials: A
authors.lastname: Galkin
mesh_terms: D016229:Amyloid beta-Peptides / Q000032:analysis* / Q000378:metabolism*; D011328:Prions / Q000032:analysis* / Q000378:metabolism*; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D060066:Protein Interaction Maps; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D011328:Prions
keywords: Alzheimer Disease; FRET; amyloid; prions; protein-protein interactions; yeast