Journal article

Formation of a high affinity lipid-binding intermediate during the early aggregation phase of alpha-synuclein

David P Smith, Deborah J Tew, Andrew F Hill, Stephen P Bottomley, Colin L Masters, Kevin J Barnham, Roberto Cappai



The alpha-synuclein (alpha-syn) protein is clearly implicated in Parkinson's disease (PD). Mutations or triplication of the alpha-syn gene leads to early onset PD, possibly by accelerating alpha-syn oligomerization. alpha-syn interacts with lipids, and this membrane binding activity may relate to its toxic activity. To understand how the alpha-syn aggregation state affects its lipid binding activity we used surface plasmon resonance to study the interaction of wild-type and mutant alpha-syn with a charged phospholipid membrane, as a function of its aggregation state. Apparent dissociation constants for alpha-syn indicated that an intermediate species, present during the lag phase of amyloid ..

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