Lipid vesicles trigger alpha-synuclein aggregation by stimulating primary nucleation

Research output: Contribution to journalJournal articleResearchpeer-review

  • Galvagnion-Büll, Céline
  • Alexander K. Buell
  • Georg Meisl
  • Thomas C. T. Michaels
  • Michele Vendruscolo
  • Tuomas P. J. Knowles
  • Christopher M. Dobson
α-Synuclein (α-syn) is a 140-residue intrinsically disordered protein that is involved in neuronal and synaptic vesicle plasticity, but its aggregation to form amyloid fibrils is the hallmark of Parkinson's disease (PD). The interaction between α-syn and lipid surfaces is believed to be a key feature for mediation of its normal function, but under other circumstances it is able to modulate amyloid fibril formation. Using a combination of experimental and theoretical approaches, we identify the mechanism through which facile aggregation of α-syn is induced under conditions where it binds a lipid bilayer, and we show that the rate of primary nucleation can be enhanced by three orders of magnitude or more under such conditions. These results reveal the key role that membrane interactions can have in triggering conversion of α-syn from its soluble state to the aggregated state that is associated with neurodegeneration and to its associated disease states.
Original languageEnglish
JournalNature Chemical Biology
Volume11
Issue number3
Pages (from-to)229-U101
ISSN1552-4450
DOIs
Publication statusPublished - Mar 2015
Externally publishedYes

ID: 216265021