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@ARTICLE{Knig:890923,
      author       = {König, Anna S. and Rösener, Nadine and Gremer, Lothar and
                      Tusche, Markus and Flender, Daniel and Reinartz, Elke and
                      Hoyer, Wolfgang and Neudecker, Philipp and Willbold, Dieter
                      and Heise, Henrike},
      title        = {{S}tructural details of amyloid β oligomers in complex
                      with human prion protein as revealed by solid-state {MAS}
                      {NMR} spectroscopy},
      journal      = {The journal of biological chemistry},
      volume       = {296},
      issn         = {0021-9258},
      address      = {Bethesda, Md.},
      publisher    = {Soc.},
      reportid     = {FZJ-2021-01248},
      pages        = {100499 -},
      year         = {2021},
      abstract     = {Human PrP (huPrP) is a high-affinity receptor for
                      oligomeric amyloid β (Aβ) protein aggregates. Binding of
                      Aβ oligomers to membrane-anchored huPrP has been suggested
                      to trigger neurotoxic cell signaling in Alzheimer’s
                      disease, while an N-terminal soluble fragment of huPrP can
                      sequester Aβ oligomers and reduce their toxicity. Synthetic
                      oligomeric Aβ species are known to be heterogeneous,
                      dynamic, and transient, rendering their structural
                      investigation particularly challenging. Here, using huPrP to
                      preserve Aβ oligomers by coprecipitating them into large
                      heteroassemblies, we investigated the conformations of
                      Aβ(1–42) oligomers and huPrP in the complex by
                      solid-state MAS NMR spectroscopy. The disordered N-terminal
                      region of huPrP becomes immobilized in the complex and
                      therefore visible in dipolar spectra without adopting
                      chemical shifts characteristic of a regular secondary
                      structure. Most of the well-defined C-terminal part of huPrP
                      is part of the rigid complex, and solid-state NMR spectra
                      suggest a loss in regular secondary structure in the two
                      C-terminal α-helices. For Aβ(1–42) oligomers in complex
                      with huPrP, secondary chemical shifts reveal substantial
                      β-strand content. Importantly, not all Aβ(1–42)
                      molecules within the complex have identical conformations.
                      Comparison with the chemical shifts of synthetic Aβ fibrils
                      suggests that the Aβ oligomer preparation represents a
                      heterogeneous mixture of β-strand-rich assemblies, of which
                      some have the potential to evolve and elongate into
                      different fibril polymorphs, reflecting a general propensity
                      of Aβ to adopt variable β-strand-rich conformers. Taken
                      together, our results reveal structural changes in huPrP
                      upon binding to Aβ oligomers that suggest a role of the C
                      terminus of huPrP in cell signaling. Trapping Aβ(1–42)
                      oligomers by binding to huPrP has proved to be a useful tool
                      for studying the structure of these highly heterogeneous
                      β-strand-rich assemblies.},
      cin          = {IBI-7},
      ddc          = {540},
      cid          = {I:(DE-Juel1)IBI-7-20200312},
      pnm          = {5244 - Information Processing in Neuronal Networks
                      (POF4-524)},
      pid          = {G:(DE-HGF)POF4-5244},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:33667547},
      UT           = {WOS:000672866400473},
      doi          = {10.1016/j.jbc.2021.100499},
      url          = {https://juser.fz-juelich.de/record/890923},
}