α-Synuclein (αSyn) is a140 amino acid (aa) amyloidogenic protein implicated in Parkinson’s disease. Its physiological functions are yet unclear, but are believed to be connected to the interaction with synaptic vesicles or membranes of other organelles. We used the fluorescence of 13 single tryptophan mutants of αSyn to determine the immersion of different positions of the protein into lipid membranes. Our results support a previously reported 3/11 helical conformation of membrane-bound αSyn determined by the presence of 11 aa repeats in the sequence, but also point to the presence of a flexible break at residues 52-54 between two helical regions. Residues 89-100 are likely disordered but interact with membranes. Deletion of the 4 aa linker between repeats does not significantly affect αSyn membrane binding but strongly decrease the protein aggregation and fibril formation propensity. We believe that the 11 aa repeats in the sequence play a key role in αSyn’s ability to switch between a helical conformation on membranes and β-sheets in fibrils.
|Journal||European biophysics journal|
|Issue number||Suppl. 1|
|Publication status||Published - 2013|
|Event||9th European Biophysics Congress, EBSA 2013 - Lisbon, Portugal|
Duration: 13 Jul 2013 → 17 Jul 2013
Conference number: 9
Shvadchak, V. V., & Subramaniam, V. (2013). Repeats in the α-synuclein sequence determine its conformation on membranes. European biophysics journal, 42(Suppl. 1), S187-S187. https://doi.org/10.1007/s00249-013-0917-x