Alterations in the brain interactome of the intrinsically disordered N-terminal domain of the cellular prion protein (PrPC) in Alzheimer's disease
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Alterations in the brain interactome of the intrinsically disordered N-terminal domain of the cellular prion protein (PrPC) in Alzheimer's disease. / Ulbrich, Sarah; Janning, Petra; Seidel, Ralf; Matschke, Jakob; Gonsberg, Anika; Jung, Sebastian; Glatzel, Markus; Engelhard, Martin; Winklhofer, Konstanze F; Tatzelt, Jörg.
in: PLOS ONE, Jahrgang 13, Nr. 5, 2018, S. e0197659.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Alterations in the brain interactome of the intrinsically disordered N-terminal domain of the cellular prion protein (PrPC) in Alzheimer's disease
AU - Ulbrich, Sarah
AU - Janning, Petra
AU - Seidel, Ralf
AU - Matschke, Jakob
AU - Gonsberg, Anika
AU - Jung, Sebastian
AU - Glatzel, Markus
AU - Engelhard, Martin
AU - Winklhofer, Konstanze F
AU - Tatzelt, Jörg
PY - 2018
Y1 - 2018
N2 - The cellular prion protein (PrPC) 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 (PrPSc), and to be crucial for the neuroprotective activity of PrPC. 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. N-PrP 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.
AB - The cellular prion protein (PrPC) 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 (PrPSc), and to be crucial for the neuroprotective activity of PrPC. 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. N-PrP 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.
KW - Acrylic Resins
KW - Aged, 80 and over
KW - Alzheimer Disease
KW - Brain
KW - Humans
KW - Male
KW - Middle Aged
KW - Polyethylene Glycols
KW - PrPC Proteins
KW - Protein Interaction Domains and Motifs
KW - Spectrometry, Mass, Electrospray Ionization
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1371/journal.pone.0197659
DO - 10.1371/journal.pone.0197659
M3 - SCORING: Journal article
C2 - 29791485
VL - 13
SP - e0197659
JO - PLOS ONE
JF - PLOS ONE
SN - 1932-6203
IS - 5
ER -
