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Biochim Biophys Acta. 2015 Sep;1848(9):1897-907. doi: 10.1016/j.bbamem.2015.01.018. Epub 2015 Feb 7.

Interactions between misfolded protein oligomers and membranes: A central topic in neurodegenerative diseases?

Author information

1
Department of Chemistry, Cambridge University, Lensfield Road, Cambridge CB2 1EW, UK; Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Gustav Wieds Vej 14, DK 8000 Aarhus C, Denmark.
2
Department of Protein Biophysics and Formulation, Biopharmaceuticals Research Unit, Novo Nordisk A/S, 2760 Måløv, Denmark.
3
Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Gustav Wieds Vej 14, DK 8000 Aarhus C, Denmark. Electronic address: dao@inano.au.dk.

Abstract

The deposition of amyloid material has been associated with many different diseases. Although these diseases are very diverse the amyloid material share many common features such as cross-β-sheet structure of the backbone of the proteins deposited. Another common feature of the aggregation process for a wide variety of proteins is the presence of prefibrillar oligomers. These oligomers are linked to the cytotoxicity occurring during the aggregation of proteins. These prefibrillar oligomers interact extensively with lipid membranes and in some cases leads to destabilization of lipid membranes. This interaction is however highly dependent on the nature of both the oligomer and the lipids. Anionic lipids are often required for interaction with the lipid membrane while increased exposure of hydrophobic patches from highly dynamic protein oligomers are structural determinants of cytotoxicity of the oligomers. To explore the oligomer lipid interaction in detail the interaction between oligomers of α-synuclein and the 4th fasciclin-1 domain of TGFBIp with lipid membranes will be examined here. For both proteins the dynamic species are the ones causing membrane destabilization and the membrane interaction is primarily seen when the lipid membranes contain anionic lipids. Hence the dynamic nature of oligomers with exposed hydrophobic patches alongside the presence of anionic lipids could be essential for the cytotoxicity observed for prefibrillar oligomers in general. This article is part of a Special Issue entitled: Lipid-protein interactions.

KEYWORDS:

Alpha-synuclein; Amyloid; Anionic lipids; Fasciclin domain; Membrane destabilization; Protein oligomer

PMID:
25666871
DOI:
10.1016/j.bbamem.2015.01.018
[Indexed for MEDLINE]
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