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Metal ions shape α-synuclein

delete2020-10-01
delete55
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OA
AI
R
Rani Moons
A
Albert Konijnenberg
C
Carl Mensch
R
Roos Van Elzen
C
Christian Johannessen
S
Stuart Maudsley
A
Anne‐Marie Lambeir
F
Frank Sobott *
DOI:10.1038/s41598-020-73207-9delete
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摘要

摘要

En 中文
alpha-Synuclein is an intrinsically disordered protein that can self-aggregate and plays a major role in Parkinson's disease (PD). Elevated levels of certain metal ions are found in protein aggregates in neurons of people suffering from PD, and environmental exposure has also been linked with neurodegeneration. Importantly, cellular interactions with metal ions, particularly Ca2+, have recently been reported as key for alpha-synuclein's physiological function at the pre-synapse. Here we study effects of metal ion interaction with alpha-synuclein at the molecular level, observing changes in the conformational behaviour of monomers, with a possible link to aggregation pathways and toxicity. Using native nano-electrospray ionisation ion mobility-mass spectrometry (nESI-IM-MS), we characterize the heterogeneous interactions of alkali, alkaline earth, transition and other metal ions and their global structural effects on alpha-synuclein. Different binding stoichiometries found upon titration with metal ions correlate with their specific binding affinity and capacity. Subtle conformational effects seen for singly charged metals differ profoundly from binding of multiply charged ions, often leading to overall compaction of the protein depending on the preferred binding sites. This study illustrates specific effects of metal coordination, and the associated electrostatic charge patterns, on the complex structural space of the intrinsically disordered protein alpha-synuclein.
Keyword:
PARKINSONS-DISEASE
ALZHEIMERS-DISEASE
AMYLOID FIBRILS
BETA-SYNUCLEIN
BINDING-SITES
PROTEIN
AGGREGATION
CATIONS
COORDINATION
FIBRILLATION
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期刊

Scientific Reports 封面图
Scientific Reports
IF:
3.9
论文数:
28.0W
被引数:
83.5W

机构

U
University of Antwerp
学者数:
2.1W
论文数: 1.9W
被引数: 2.6W
U
university of leeds
学者数:
3.6W
论文数: 3.3W
被引数: 45
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