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Zn(II) binding caus...
Zn(II) binding causes interdomain changes in the structure and flexibility of the human prion protein
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Gielnik, Maciej (författare)
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Taube, Michał (författare)
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Zhukova, Lilia (författare)
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Zhukov, Igor (författare)
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- Wärmländer, Sebastian K. T. S. (författare)
- Stockholms universitet,Institutionen för biokemi och biofysik
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Svedružić, Željko (författare)
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Kwiatek, Wojciech M. (författare)
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- Gräslund, Astrid (författare)
- Stockholms universitet,Institutionen för biokemi och biofysik
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Kozak, Maciej (författare)
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(creator_code:org_t)
- 2021-11-04
- 2021
- Engelska.
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
- Relaterad länk:
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https://doi.org/10.1...
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https://www.nature.c...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- The cellular prion protein (PrP(C)) is a mainly alpha-helical 208-residue protein located in the pre- and postsynaptic membranes. For unknown reasons, PrP(C) can undergo a structural transition into a toxic, beta-sheet rich scrapie isoform (PrPSc) that is responsible for transmissible spongiform encephalopathies (TSEs). Metal ions seem to play an important role in the structural conversion. PrP(C) binds Zn(II) ions and may be involved in metal ion transport and zinc homeostasis. Here, we use multiple biophysical techniques including optical and NMR spectroscopy, molecular dynamics simulations, and small angle X-ray scattering to characterize interactions between human PrP(C) and Zn(II) ions. Binding of a single Zn(II) ion to the PrP(C) N-terminal domain via four His residues from the octarepeat region induces a structural transition in the C-terminal alpha-helices 2 and 3, promotes interaction between the N-terminal and C-terminal domains, reduces the folded protein size, and modifies the internal structural dynamics. As our results suggest that PrP(C) can bind Zn(II) under physiological conditions, these effects could be important for the physiological function of PrP(C).
Ämnesord
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
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- ref (ämneskategori)
- art (ämneskategori)
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