Synaptic vesicle mimics affect the aggregation of wild-type and A53T α-synuclein variants differently albeit similar membrane affinity
Journal article, 2019

Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: 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. © The Author(s) 2019.

amyloid fibrils

membrane-bound α-synuclein

protein aggregation

small unilamellar vesicles

kinetic profiles


Sandra Rocha

Chalmers, Biology and Biological Engineering, Chemical Biology

Ranjeet Kumar

Chalmers, Biology and Biological Engineering, Chemical Biology

Istvan Horvath

Chalmers, Biology and Biological Engineering, Chemical Biology

Pernilla Wittung Stafshede

Chalmers, Biology and Biological Engineering, Chemical Biology

Protein engineering, design & selection : PEDS

17410126 (ISSN) 17410134 (eISSN)

Vol. 32 2 59-66

Subject Categories

Biochemistry and Molecular Biology


Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)





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