Remodeling of Lipid Vesicles into Cylindrical Micelles by α-Synuclein in an Extended α-Helical Conformation

Abstract

Background: Membrane fusion and fission events are effected by remodeling proteins. Results: Using cryoelectron microscopy, we observed the conversion of large spherical lipid vesicles into narrow protein-coated tubes. Conclusion: Tubulation is accompanied by ␣-synuclein switching into an extended ␣-helical conformation. Significance: The cylindrical micelles produced resemble a hemi-fission/fusion state of the membrane.

α-Synuclein Senses Lipid Packing Defects and Induces Lateral Expansion of Lipids Leading to Membrane Remodeling

“…The lack of evident remodeling of complete bilayers can be attributed to the rapidity of a limited remodeling process (just a lateral expansion of lipids) for DOPC/DOPE/DOPS (20:50:30), which can be faster than the lag time between the addition of the protein to the SLB Lateral expansion of the lipids induces a void in the bilayer core that rearranges to minimize the energy. Membrane remodeling processes range from membrane thinning to expansion of lipids out of the membrane plane and a curvature-generating process, as reported previously (28,59). B, a planar lamellar bilayer with a high content of cone-shaped lipids.…”

“…8, which is based on results obtained in the present study and also those reported in the literature (10,26,28,59). Lipid membranes are dynamic structures, and, under appropriate conditions of lipid composition and bilayer structure, they enable protein insertion to occur.…”

N-terminal Acetylation Stabilizes N-terminal Helicity in Lipid- and Micelle-bound α-Synuclein and Increases Its Affinity for Physiological Membranes

“…Nevertheless, it has been shown that curvature selectivity by aSyn cannot be comprehensively characterized through measurements of affinity alone (54), and further studies will be required to evaluate more directly the curvature selectivity of Ac-aSyn. In addition, it is now generally accepted that aSyn can influence membrane properties, specifically curvature, in addition to sensing them (57,58,60,62,63,66,75,83), and the influence of N-terminal acetylation on this activity of the protein remains to be explored.…”

Membrane Curvature-sensing and Curvature-inducing Activity of Islet Amyloid Polypeptide and Its Implications for Membrane Disruption

“…Examples include the H0 ␣-helices of N-BAR domain proteins such as amphiphysin and endophilin (44 -51). In addition, ␣-synuclein binds to negatively charged membranes as an amphipathic ␣-helix that alone is sufficient to induce membrane curvature, or in other words to remodel liposomes into tubular structures, small, highly curved vesicles, or protein-lipid nanoparticles (52)(53)(54)(55). Importantly, such membrane remodeling and induction of membrane curvature can cause disruption of membrane integrity (52).…”