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Structural basis fo...
Structural basis for dityrosine-mediated inhibition of alpha-synuclein fibrillation
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Sahin, Cagla (author)
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Østerlund, Eva C (author)
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- Costeira-Paulo, Joana, 1993- (author)
- Uppsala universitet,Biokemi,Marklund group
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Österlund, Nicklas (author)
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Pedersen, Jannik N (author)
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Christiansen, Gunna (author)
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Nielsen, Janni (author)
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Grønnemose, Anne L (author)
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Amstrup, Søren K (author)
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Tiwari, Manish K (author)
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Bjerrum, Morten J (author)
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Ilag, Leopold L (author)
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Davies, Michael J (author)
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Pedersen, Jan S (author)
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- Marklund, Erik G (author)
- Uppsala universitet,Biokemi,Marklund group
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Landreh, Michael (author)
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Møller, Ian M (author)
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Jørgensen, Thomas J D (author)
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Otzen, Daniel E (author)
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(creator_code:org_t)
- English.
- Related links:
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https://urn.kb.se/re...
Abstract
Subject headings
Close
- α-synuclein (aSyn) is a small intrinsically disordered protein which can self-assemble into highly organized β-sheet structures that are found to accumulate in plaques in the brain of Parkinson’s Disease patients. Oxidative stress has been shown to be important for aSyn and its self-assembly. Here we characterize the molecular and structural effects that mild oxidation has on aSyn monomer and its aggregation. Using a combination of biophysical methods, SAXS and native ion mobility mass spectrometry, we find that oxidation leads to formation of intramolecular dityrosine cross-linkages that reduce aSyn’s size by a factor of √2. MD simulations support our experimental results showing a stable and compact aSyn conformation that prevents self-assembly and amyloid formation by steric hindrance, suggesting an important role of mild oxidation in preventing amyloid formation.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Keyword
- Parkinson’s Disease
- Disorder
- amyloid
- dityrosine crosslinks
- metal catalyzed oxidation
- Biokemi
- Biochemistry
Publication and Content Type
- vet (subject category)
- ovr (subject category)
To the university's database
- By the author/editor
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Sahin, Cagla
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Østerlund, Eva C
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Costeira-Paulo, ...
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Österlund, Nickl ...
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Pedersen, Jannik ...
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Christiansen, Gu ...
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show more...
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Nielsen, Janni
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Grønnemose, Anne ...
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Amstrup, Søren K
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Tiwari, Manish K
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Bjerrum, Morten ...
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Ilag, Leopold L
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Davies, Michael ...
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Pedersen, Jan S
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Marklund, Erik G
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Landreh, Michael
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Møller, Ian M
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Jørgensen, Thoma ...
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Otzen, Daniel E
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show less...
- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Biochemistry and ...
- By the university
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Uppsala University