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Interaction between...
Interaction between Copper Chaperone Atox1 and Parkinson's Disease Protein α-Synuclein Includes Metal-Binding Sites and Occurs in Living Cells
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- Horvath, Istvan, 1979 (författare)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Blockhuys, Stephanie, 1983 (författare)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Šulskis, Darius (författare)
- Göteborgs universitet,University of Gothenburg
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- Holgersson, Stellan, 1964 (författare)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Kumar, Ranjeet, 1980 (författare)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Burmann, Björn M. (författare)
- Göteborgs universitet,University of Gothenburg
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- Wittung Stafshede, Pernilla, 1968 (författare)
- Chalmers tekniska högskola,Chalmers University of Technology
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(creator_code:org_t)
- 2019-10-10
- 2019
- Engelska.
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Ingår i: ACS Chemical Neuroscience. - : American Chemical Society (ACS). - 1948-7193. ; 10:11, s. 4659-4668
- Relaterad länk:
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https://research.cha...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Alterations in copper ion homeostasis appear coupled to neurodegenerative disorders, but mechanisms are unknown. The cytoplasmic copper chaperone Atox1 was recently found to inhibit amyloid formation in vitro of α-synuclein, the amyloidogenic protein in Parkinson's disease. As α-synuclein may have copper-dependent functions, and free copper ions promote α-synuclein amyloid formation, it is important to characterize the Atox1 interaction with α-synuclein on a molecular level. Here we applied solution-state nuclear magnetic resonance spectroscopy, with isotopically labeled α-synuclein and Atox1, to define interaction regions in both proteins. The α-synuclein interaction interface includes the whole N-terminal part up to Gln24; in Atox1, residues around the copper-binding cysteines (positions 11-16) are mostly perturbed, but additional effects are also found for residues elsewhere in both proteins. Because α-synuclein is N-terminally acetylated in vivo, we established that Atox1 also inhibits amyloid formation of this variant in vitro, and proximity ligation in human cell lines demonstrated α-synuclein-Atox1 interactions in situ. Thus, this interaction may provide the direct link between copper homeostasis and amyloid formation in vivo.
Ämnesord
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biofysik (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biophysics (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
Nyckelord
- proximity ligation assay
- Parkinson's disease
- Atox1
- protein-protein interaction
- nuclear magnetic resonance
- α-Synuclein
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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