Differential phospholipid binding of alpha-synuclein variants implicated in Parkinson's disease revealed by solution NMR spectroscopy.

ABSTRACT: Three familial variants of the presynaptic protein alpha-synuclein (alphaS), A30P, E46K, and A53T, correlate with rare inherited Parkinson's disease (PD), while wild-type alphaS is implicated in sporadic PD. The classic manifestation of both familiar and sporadic PD is the formation of fibrillar structures of alphaS which accumulate as the main component in intraneuronal Lewy bodies. At presynaptic termini, the partitioning of alphaS between disordered cytosolic and membrane-bound states likely mediates its proposed role in regulation of reserve pools of synaptic vesicles. Previously, we reported on multiple distinct phospholipid binding modes of alphaS with slow binding kinetics. Here, we report the phospholipid binding properties of the disease variants, viewed by solution NMR in a resid

SUBMITTER: Bodner CR 

PROVIDER: S-EPMC2815556 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature