Dataset Information

Amyloids of alpha-synuclein affect the structure and dynamics of supported lipid bilayers.

ABSTRACT: Interactions of monomeric alpha-synuclein (?S) with lipid membranes have been suggested to play an important role in initiating aggregation of ?S. We have systematically analyzed the distribution and self-assembly of monomeric ?S on supported lipid bilayers. We observe that at protein/lipid ratios higher than 1:10, ?S forms micrometer-sized clusters, leading to observable membrane defects and decrease in lateral diffusion of both lipids and proteins. An ?S deletion mutant lacking amino-acid residues 71-82 binds to membranes, but does not observably affect membrane integrity. Although this deletion mutant cannot form amyloid, significant amyloid formation is observed in the wild-type ?S clusters. These results suggest that the process of amyloid formation, rather than binding of ?S on membranes, is crucial in compromising membrane integrity.

SUBMITTER: Iyer A

PROVIDER: S-EPMC4070068 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Amyloids of alpha-synuclein affect the structure and dynamics of supported lipid bilayers.

Iyer Aditya A Petersen Nils O NO Claessens Mireille M A E MM Subramaniam Vinod V

Biophysical journal 20140601 12

Interactions of monomeric alpha-synuclein (αS) with lipid membranes have been suggested to play an important role in initiating aggregation of αS. We have systematically analyzed the distribution and self-assembly of monomeric αS on supported lipid bilayers. We observe that at protein/lipid ratios higher than 1:10, αS forms micrometer-sized clusters, leading to observable membrane defects and decrease in lateral diffusion of both lipids and proteins. An αS deletion mutant lacking amino-acid resi ...[more]

PMID: 24940776

Similar Datasets

Project description:An amyloid form of the protein ?-synuclein is the major component of the intraneuronal inclusions called Lewy bodies, which are the neuropathological hallmark of Parkinson's disease (PD). ?-Synuclein is known to associate with anionic lipid membranes, and interactions between aggregating ?-synuclein and cellular membranes are thought to be important for PD pathology. We have studied the molecular determinants for adsorption of monomeric ?-synuclein to planar model lipid membranes composed of zwitterionic phosphatidylcholine alone or in a mixture with anionic phosphatidylserine (relevant for plasma membranes) or anionic cardiolipin (relevant for mitochondrial membranes). We studied the adsorption of the protein to supported bilayers, the position of the protein within and outside the bilayer, and structural changes in the model membranes using two complementary techniques-quartz crystal microbalance with dissipation monitoring, and neutron reflectometry. We found that the interaction and adsorbed conformation depend on membrane charge, protein charge, and electrostatic screening. The results imply that ?-synuclein adsorbs in the headgroup region of anionic lipid bilayers with extensions into the bulk but does not penetrate deeply into or across the hydrophobic acyl chain region. The adsorption to anionic bilayers leads to a small perturbation of the acyl chain packing that is independent of anionic headgroup identity. We also explored the effect of changing the area per headgroup in the lipid bilayer by comparing model systems with different degrees of acyl chain saturation. An increase in area per lipid headgroup leads to an increase in the level of ?-synuclein adsorption with a reduced water content in the acyl chain layer. In conclusion, the association of ?-synuclein to membranes and its adsorbed conformation are of electrostatic origin, combined with van der Waals interactions, but with a very weak correlation to the molecular structure of the anionic lipid headgroup. The perturbation of the acyl chain packing upon monomeric protein adsorption favors association with unsaturated phospholipids preferentially found in the neuronal membrane.

Dataset Information

Amyloids of alpha-synuclein affect the structure and dynamics of supported lipid bilayers.

Publications

Amyloids of alpha-synuclein affect the structure and dynamics of supported lipid bilayers.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets