Jump to main content
Jump to site search
SCHEDULED MAINTENANCE Close the message box

Maintenance work is planned for Monday 16 August 2021 from 07:00 to 23:59 (BST).

Website performance may be temporarily affected and you may not be able to access some PDFs or images. If this does happen, refreshing your web browser should resolve the issue. We apologise for any inconvenience this might cause and thank you for your patience.


Issue 24, 2015

Methyl-branched lipids promote the membrane adsorption of α-synuclein by enhancing shallow lipid-packing defects

Author affiliations

Abstract

Alpha-synuclein (AS) is a synaptic protein that is directly involved in Parkinson's disease due to its tendency to form protein aggregates. Since AS aggregation can be dependent on the interactions between the protein and the cell plasma membrane, elucidating the membrane binding properties of AS is of crucial importance to establish the molecular basis of AS aggregation into toxic fibrils. Using a combination of in vitro reconstitution experiments based on Giant Unilamellar Vesicles (GUVs), confocal microscopy and all-atom molecular dynamics simulations, we have investigated the membrane binding properties of AS, with a focus on the relative contribution of hydrophobic versus electrostatic interactions. In contrast with previous observations, we did not observe any binding of AS to membranes containing the ganglioside GM1, even at relatively high GM1 content. AS, on the other hand, showed a stronger affinity for neutral flat membranes consisting of methyl-branched lipids. To rationalize these results, we used all-atom molecular dynamics simulations to investigate the influence of methyl-branched lipids on interfacial membrane properties. We found that methyl-branched lipids promote the membrane adsorption of AS by creating shallow lipid-packing defects to a larger extent than polyunsaturated and monounsaturated lipids. Our findings suggest that methyl-branched lipids may constitute a remarkably adhesive substrate for peripheral proteins that adsorb on membranes via hydrophobic insertions.

Graphical abstract: Methyl-branched lipids promote the membrane adsorption of α-synuclein by enhancing shallow lipid-packing defects

Article information


Submitted
15 Jan 2015
Accepted
17 Mar 2015
First published
23 Mar 2015

Phys. Chem. Chem. Phys., 2015,17, 15589-15597
Article type
Paper

Methyl-branched lipids promote the membrane adsorption of α-synuclein by enhancing shallow lipid-packing defects

M. Garten, C. Prévost, C. Cadart, R. Gautier, L. Bousset, R. Melki, P. Bassereau and S. Vanni, Phys. Chem. Chem. Phys., 2015, 17, 15589 DOI: 10.1039/C5CP00244C

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.


Social activity

Search articles by author

Spotlight

Advertisements