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Membrane Lipid Co-Aggregation with α-Synuclein Fibrils
Amyloid deposits from several human diseases have been found to contain membrane lipids. Co-aggregation of lipids and amyloid proteins in amyloid aggregates, and the related extraction of lipids from cellular membranes, can influence structure and function in both the membrane and the formed amyloid...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3795653/ https://www.ncbi.nlm.nih.gov/pubmed/24146972 http://dx.doi.org/10.1371/journal.pone.0077235 |
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author | Hellstrand, Erik Nowacka, Agnieszka Topgaard, Daniel Linse, Sara Sparr, Emma |
author_facet | Hellstrand, Erik Nowacka, Agnieszka Topgaard, Daniel Linse, Sara Sparr, Emma |
author_sort | Hellstrand, Erik |
collection | PubMed |
description | Amyloid deposits from several human diseases have been found to contain membrane lipids. Co-aggregation of lipids and amyloid proteins in amyloid aggregates, and the related extraction of lipids from cellular membranes, can influence structure and function in both the membrane and the formed amyloid deposit. Co-aggregation can therefore have important implications for the pathological consequences of amyloid formation. Still, very little is known about the mechanism behind co-aggregation and molecular structure in the formed aggregates. To address this, we study in vitro co-aggregation by incubating phospholipid model membranes with the Parkinson’s disease-associated protein, α-synuclein, in monomeric form. After aggregation, we find spontaneous uptake of phospholipids from anionic model membranes into the amyloid fibrils. Phospholipid quantification, polarization transfer solid-state NMR and cryo-TEM together reveal co-aggregation of phospholipids and α-synuclein in a saturable manner with a strong dependence on lipid composition. At low lipid to protein ratios, there is a close association of phospholipids to the fibril structure, which is apparent from reduced phospholipid mobility and morphological changes in fibril bundling. At higher lipid to protein ratios, additional vesicles adsorb along the fibrils. While interactions between lipids and amyloid-protein are generally discussed within the perspective of different protein species adsorbing to and perturbing the lipid membrane, the current work reveals amyloid formation in the presence of lipids as a co-aggregation process. The interaction leads to the formation of lipid-protein co-aggregates with distinct structure, dynamics and morphology compared to assemblies formed by either lipid or protein alone. |
format | Online Article Text |
id | pubmed-3795653 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-37956532013-10-21 Membrane Lipid Co-Aggregation with α-Synuclein Fibrils Hellstrand, Erik Nowacka, Agnieszka Topgaard, Daniel Linse, Sara Sparr, Emma PLoS One Research Article Amyloid deposits from several human diseases have been found to contain membrane lipids. Co-aggregation of lipids and amyloid proteins in amyloid aggregates, and the related extraction of lipids from cellular membranes, can influence structure and function in both the membrane and the formed amyloid deposit. Co-aggregation can therefore have important implications for the pathological consequences of amyloid formation. Still, very little is known about the mechanism behind co-aggregation and molecular structure in the formed aggregates. To address this, we study in vitro co-aggregation by incubating phospholipid model membranes with the Parkinson’s disease-associated protein, α-synuclein, in monomeric form. After aggregation, we find spontaneous uptake of phospholipids from anionic model membranes into the amyloid fibrils. Phospholipid quantification, polarization transfer solid-state NMR and cryo-TEM together reveal co-aggregation of phospholipids and α-synuclein in a saturable manner with a strong dependence on lipid composition. At low lipid to protein ratios, there is a close association of phospholipids to the fibril structure, which is apparent from reduced phospholipid mobility and morphological changes in fibril bundling. At higher lipid to protein ratios, additional vesicles adsorb along the fibrils. While interactions between lipids and amyloid-protein are generally discussed within the perspective of different protein species adsorbing to and perturbing the lipid membrane, the current work reveals amyloid formation in the presence of lipids as a co-aggregation process. The interaction leads to the formation of lipid-protein co-aggregates with distinct structure, dynamics and morphology compared to assemblies formed by either lipid or protein alone. Public Library of Science 2013-10-11 /pmc/articles/PMC3795653/ /pubmed/24146972 http://dx.doi.org/10.1371/journal.pone.0077235 Text en © 2013 Hellstrand et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Hellstrand, Erik Nowacka, Agnieszka Topgaard, Daniel Linse, Sara Sparr, Emma Membrane Lipid Co-Aggregation with α-Synuclein Fibrils |
title | Membrane Lipid Co-Aggregation with α-Synuclein Fibrils |
title_full | Membrane Lipid Co-Aggregation with α-Synuclein Fibrils |
title_fullStr | Membrane Lipid Co-Aggregation with α-Synuclein Fibrils |
title_full_unstemmed | Membrane Lipid Co-Aggregation with α-Synuclein Fibrils |
title_short | Membrane Lipid Co-Aggregation with α-Synuclein Fibrils |
title_sort | membrane lipid co-aggregation with α-synuclein fibrils |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3795653/ https://www.ncbi.nlm.nih.gov/pubmed/24146972 http://dx.doi.org/10.1371/journal.pone.0077235 |
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