Orientation of α-Synuclein at Negatively Charged Lipid Vesicles: Linear Dichroism Reveals Time-Dependent Changes in Helix Binding Mode
Journal article, 2021

The neuronal protein α-synuclein, linked to Parkinson's disease, binds to negatively charged vesicles adopting a partial α-helix structure, but helix arrangement at the vesicle surface is not fully understood. Using linear dichroism spectroscopy (LD), we study the interaction of monomeric α-synuclein with large unilamellar vesicles of 1,2-dioleoyl-sn-glycero-3-phospho-l-serine (DOPS), 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-l-serine (POPS), and 1,2-dioleoyl-sn-glycero-3-phospho-(1′-rac-glycerol) (DOPG) under mild shear flow. The LD data of oriented lipid vesicles show that the long axis of the protein helix is oriented preferentially perpendicular to the membrane normal but deviates from a uniform in-plane distribution. Upon initial binding, a fraction of helices are oriented in the direction of least curvature for all ellipsoid-shaped vesicles at a lipid:protein molar ratio of 100. However, at a lower protein concentration the helices distribute uniformly on DOPS and POPS vesicles. In all cases, the α-synuclein helices rearrange with time (minute time scale) in the shear flow and begin to tilt into the vesicle membrane. Faster reorientation kinetics in the presence of flow suggests that modulation of membrane dynamics, by thermal or shear-dynamic activation, may overcome steric barriers by what may be called "flow catalysis".


Sandra Rocha

Chalmers, Biology and Biological Engineering, Chemical Biology

Ranjeet Kumar

Chalmers, Biology and Biological Engineering, Chemical Biology

Bengt Nordén

Chalmers, Chemistry and Chemical Engineering, Chemistry and Biochemistry

Pernilla Wittung Stafshede

Chalmers, Biology and Biological Engineering, Chemical Biology

Journal of the American Chemical Society

0002-7863 (ISSN) 1520-5126 (eISSN)

Vol. 143 45 18899-18906

Subject Categories

Physical Chemistry

Biochemistry and Molecular Biology






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4/5/2022 5