The study investigates the interaction between α-synuclein, a highly conserved presynaptic protein, and phospholipid bilayers. α-Synuclein is associated with Parkinson's and Alzheimer's diseases, and its sequence contains degenerate 11-residue repeats reminiscent of amphipathic α-helical domains found in apolipoproteins. The researchers hypothesized that α-synuclein would bind to phospholipid bilayers and that this binding would stabilize its α-helical secondary structure. They found that α-synuclein binds preferentially to small unilamellar vesicles containing acidic phospholipids, with a preference for vesicles of 20–25 nm diameter over larger vesicles. Lipid binding increased α-helicity from 3% to approximately 80%. These findings suggest that α-synuclein's secondary structure is sufficient to target it to specific vesicles in the presynaptic terminal, potentially facilitating selective regulation of vesicle function. The study also discusses the implications of these findings for understanding the role of α-synuclein in neurodegenerative diseases.The study investigates the interaction between α-synuclein, a highly conserved presynaptic protein, and phospholipid bilayers. α-Synuclein is associated with Parkinson's and Alzheimer's diseases, and its sequence contains degenerate 11-residue repeats reminiscent of amphipathic α-helical domains found in apolipoproteins. The researchers hypothesized that α-synuclein would bind to phospholipid bilayers and that this binding would stabilize its α-helical secondary structure. They found that α-synuclein binds preferentially to small unilamellar vesicles containing acidic phospholipids, with a preference for vesicles of 20–25 nm diameter over larger vesicles. Lipid binding increased α-helicity from 3% to approximately 80%. These findings suggest that α-synuclein's secondary structure is sufficient to target it to specific vesicles in the presynaptic terminal, potentially facilitating selective regulation of vesicle function. The study also discusses the implications of these findings for understanding the role of α-synuclein in neurodegenerative diseases.