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Synaptic vesicle mimics affect the aggregation of wild-type and A53T α-synuclein variants differently albeit similar membrane affinity
- Source :
- Protein Engineering, Design and Selection
- Publication Year :
- 2019
- Publisher :
- Oxford University Press, 2019.
-
Abstract
- α-Synuclein misfolding results in the accumulation of amyloid fibrils in Parkinson’s disease. Missense protein mutations (e.g. A53T) have been linked to early onset disease. Although α-synuclein interacts with synaptic vesicles in the brain, it is not clear what role they play in the protein aggregation process. Here, we compare the effect of small unilamellar vesicles (lipid composition similar to synaptic vesicles) on wild-type (WT) and A53T α-synuclein aggregation. Using biophysical techniques, we reveal that binding affinity to the vesicles is similar for the two proteins, and both interact with the helix long axis parallel to the membrane surface. Still, the vesicles affect the aggregation of the variants differently: effects on secondary processes such as fragmentation dominate for WT, whereas for A53T, fibril elongation is mostly affected. We speculate that vesicle interactions with aggregate intermediate species, in addition to monomer binding, vary between WT and A53T, resulting in different consequences for amyloid formation.
- Subjects :
- Amyloid
small unilamellar vesicles
Bioengineering
Protein aggregation
010402 general chemistry
Fibril
01 natural sciences
Biochemistry
Synaptic vesicle
protein aggregation
03 medical and health sciences
amyloid fibrils
Protein Aggregates
kinetic profiles
Fragmentation (cell biology)
Molecular Biology
Unilamellar Liposomes
030304 developmental biology
0303 health sciences
Chemistry
Vesicle
Cell Membrane
Wild type
membrane-bound α-synuclein
0104 chemical sciences
Membrane
Mutation
Biophysics
alpha-Synuclein
Original Article
Mutant Proteins
Synaptic Vesicles
Biotechnology
Protein Binding
Subjects
Details
- Language :
- English
- ISSN :
- 17410134 and 17410126
- Volume :
- 32
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Protein Engineering, Design and Selection
- Accession number :
- edsair.doi.dedup.....6ff05c8f8caa5aefccfb6fbb2dc25ac1