Comparison of apha-synuclein and amyloid beta membrane interactions

SHVADCHAK VV; FALOMIR LOCKHART LJ; YUSHCHENKO DA; MELY Y; JOVIN TM

San Diego

Congreso; 56th BPS Meeting - San Diego; 2012

BPS - UCSD

alpha-synuclein (aSyn) and amyloid beta (1-42) peptide (Abeta) are the main constituents of pathological deposits in the midbrain of individuals affected by Parkinson’s disease and Alzheimer’s disease respectively. Defining the interactions of aSyn and Abeta with membranes is essential for understanding the neurotoxicity caused by mutations and/or overexpression. We performed a systematic in vitro study of the effects of membrane charge, phase, curvature, defects and lipid unsaturation on aSyn and Abeta binding using model vesicles and proteins labeled with a new solvatochromic fluorescent probe. The probe’s emission spectrum strongly depends on the membrane properties, allowing clear discrimination of the protein bound to vesicles of different composition that enables measurements of the kinetics of aSyn migration between membranes of different compositions [1]. The nteraction of aSyn with vesicular membranes is fast and reversible while the membrane binding of Abeta is mainly kinetically controlled and competes with aggregation. By introducing the probe at different positions of aSyn and Abeta we were able to estimate the relative immersion of different protein domains into membrane, and its changes depending on membrane composition and lipid-to-protein ratio.