Interaction of α-Synuclein with Negatively Charged Lipid Membranes Monitored by Surface Plasmon Resonance

Abstract

Aggregation of presynaptic protein α-synuclein is implicated in the development of Parkinson's disease. Interaction of α-synuclein with lipid membranes appears to be critical for its physiological and pathological roles. Anionic lipids trigger conformational transition of α-synuclein from its natively disordered into an α-helical structure. Here we used surface plasmon resonance (SPR) to determine the affinities of α-synuclein for the small unilamellar vesicles composed of anionic 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-L-serine (POPS) or 1,2-dipalmitoyl-sn-glycero-3-phosphoglycerol (DPPG) and neutral 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipids. α-Synuclein bound in a concentration dependent manner to equimolar mixtures of POPC/POPS and POPC/DPPG vesicles. The affinity of α-synuclein for POPC/POPS was ~3 -fold higher than for POPC/DPPG. These results indicate that headgroup charge is not the only factor contributing to α-synuclein-membrane association.

Interaction of α‐Synuclein with Phospholipids and the Associated Restructuring of Interfacial Lipid Water: An Interface‐Selective Vibrational Spectroscopic Study

“…[7][8][9]11] Fore xample,a ggregation is more pronounced at the surface of negatively charged lipids than that of the positively charged and zwitterionic lipids.F or af ixed concentration of monomeric aS, the aggregation increases linearly with the concentration of negatively charged lipid. [9,14] However,i ti si ntriguing to observe that an egatively charged lipid surface promotes the aggregation of an et negatively charged (À9) protein which is supposed to be repelled from the membrane surface.…”

Interaction of α‐Synuclein with Phospholipids and the Associated Restructuring of Interfacial Lipid Water: An Interface‐Selective Vibrational Spectroscopic Study

“…[7][8][9]11] Fore xample,a ggregation is more pronounced at the surface of negatively charged lipids than that of the positively charged and zwitterionic lipids.F or af ixed concentration of monomeric aS, the aggregation increases linearly with the concentration of negatively charged lipid. [9,14] However,i ti si ntriguing to observe that an egatively charged lipid surface promotes the aggregation of an et negatively charged (À9) protein which is supposed to be repelled from the membrane surface.…”