- The cellular prion protein (PrP\(^{C}\)) is implicated in neuroprotective signaling and neurotoxic pathways in both prion diseases and Alzheimer's disease (AD). Specifically, the intrinsically disordered N-terminal domain (N-PrP) has been shown to interact with neurotoxic ligands, such as Aβ and Scrapie prion protein (PrP\(^{Sc}\)), and to be crucial for the neuroprotective activity of PrP\(^{C}\). To gain further insight into cellular pathways tied to PrP, we analyzed the brain interactome of N-PrP. As a novel approach employing recombinantly expressed PrP and intein-mediated protein ligation, we used N-PrP covalently coupled to beads as a bait for affinity purification. N-PrP beads were incubated with human AD or control brain lysates. NPrP binding partners were then identified by electrospray ionization tandem mass spectrometry (nano ESI-MS/MS). In addition to newly identified proteins we found many previously described PrP interactors, indicating a crucial role of the intrinsically disordered part of PrP in mediating protein interactions. Moreover, some interactors were found only in either non-AD or AD brain, suggesting aberrant PrPC interactions in the pathogenesis of AD.
MetadatenAuthor: | Sarah Ines UlbrichGND, Petra JanningGND, Ralf SeidelGND, Jakob MatschkeGND, Anika GonsbergGND, Sebastian JungORCiDGND, Markus GlatzelORCiDGND, Martin EngelhardGND, Konstanze WinklhoferORCiDGND, Jörg TatzeltORCiDGND |
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URN: | urn:nbn:de:hbz:294-62905 |
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DOI: | https://doi.org/10.1371/journal.pone.0197659 |
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Parent Title (English): | PLoS ONE |
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Document Type: | Article |
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Language: | English |
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Date of Publication (online): | 2019/02/22 |
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Date of first Publication: | 2018/05/23 |
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Publishing Institution: | Ruhr-Universität Bochum, Universitätsbibliothek |
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Tag: | Open Access Fonds |
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Volume: | 13 |
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Issue: | 5 |
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First Page: | e019765-1 |
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Last Page: | e019765-15 |
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Note: | PLoS ONE, Bd. 13.2018, H. 5, Artikelnummer e019765 |
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Note: | Article Processing Charge funded by the Deutsche Forschungsgemeinschaft (DFG) and the Open Access Publication Fund of Ruhr-Universität Bochum. |
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Institutes/Facilities: | Institut für Biochemie und Pathobiochemie, Abteilung Biochemie Neurodegenerativer Erkrankungen |
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Dewey Decimal Classification: | Technik, Medizin, angewandte Wissenschaften / Medizin, Gesundheit |
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open_access (DINI-Set): | open_access |
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faculties: | Medizinische Fakultät |
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Licence (English): | Creative Commons - CC BY 4.0 - Attribution 4.0 International |
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