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Interaction between...
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Horvath, Istvan,1979Chalmers tekniska högskola,Chalmers University of Technology
(författare)
Interaction between Copper Chaperone Atox1 and Parkinson's Disease Protein α-Synuclein Includes Metal-Binding Sites and Occurs in Living Cells
- Artikel/kapitelEngelska2019
Förlag, utgivningsår, omfång ...
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2019-10-10
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American Chemical Society (ACS),2019
Nummerbeteckningar
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LIBRIS-ID:oai:research.chalmers.se:074c70ea-5a29-49b7-be3c-f3173faee648
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https://research.chalmers.se/publication/513667URI
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https://doi.org/10.1021/acschemneuro.9b00476DOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:art swepub-publicationtype
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Ämneskategori:ref swepub-contenttype
Anmärkningar
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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 och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Blockhuys, Stephanie,1983Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)steblo
(författare)
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Šulskis, DariusGöteborgs universitet,University of Gothenburg
(författare)
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Holgersson, Stellan,1964Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)stehol
(författare)
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Kumar, Ranjeet,1980Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)ranjeet
(författare)
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Burmann, Björn M.Göteborgs universitet,University of Gothenburg
(författare)
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Wittung Stafshede, Pernilla,1968Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)perwit
(författare)
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Chalmers tekniska högskolaGöteborgs universitet
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:ACS Chemical Neuroscience: American Chemical Society (ACS)10:11, s. 4659-46681948-7193
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