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

Abstract

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