Study of the Interaction of Segmental Peptides of α-Synuclein with Phospholipid by Langmuir Monolayer and Surface FT-IR Technique

Abstract

α-Synuclein (α-syn), which is a protein contains 140 amino acid residues, is the major protein component of Lewy bodies, the hall mark deposition of Parkinson’s disease (PD).1 Segment peptides of α-syn was also detected in Lewy bodies together with phospholipids. Despite the abundance (~ 1 % among the total proteins) in the brain, α-syn accumulates in the presynaptic terminals where exists high concentration of amphiphilic structure (e.g., liposomes and cell membrane) comprising phospholipids.2 Therefore, it is important to study the interaction between α-syn segmental peptides and phospholipids. Previously, α-syn has been spread at the air-water interface by Langmuir monolayer technique which was used to mimic the amphiphilic nature in vivo.3 Spectroscopic and surface FTIR results showed that α-syn transformed from unstructured conformation in aqueous solution to α-helix at the interface in a monolayer structure. Here, the interaction of phospholipid with several segmental peptides of α-syn by spreading phospholipid at the interface to form monolayer in the presence of several segmental peptides of α-syn. From surface FTIR results, the tilted angle of the alkyl chain in the pure phospholipid monolayer is 79º±1o. Among segmental peptides, three longer peptides (i.e., α-syn(66-85), α-syn(61-95), and α-syn(57-102)), which can form Langmuir monolayer by themselves, were found not to interact substantially with phospholipid because the titled angle of alkyl chain of phospholipids keeps at 79º±1o. Differently, a shorter segmental peptide α-syn(71-82) interacts with phospholipids intensively and changes the tilted angle of alkyl chain of phospholipid to 76º±1o.