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Cholesterol and anionic phospholipids increase the binding of amyloidogenic transthyretin to lipid membranes

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Hou, X and Mechler, A and Martin, LL and Aguilar, MI and Small, DH (2008) Cholesterol and anionic phospholipids increase the binding of amyloidogenic transthyretin to lipid membranes. Biochimica et Biophysica Acta - Biomembranes, 1778 (1). pp. 198-205. ISSN 0005-2736

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Abstract

Deposition of transthyretin (TTR) amyloid is a pathological hallmark of familial amyloidotic polyneuropathy (FAP). Recently we showed that TTR binds to membrane lipids via electrostatic interactions and that membrane binding is correlated with the cytotoxicity induced by amyloidogenic TTR. In the present study, we examined the role of lipid composition in membrane binding of TTR by a surface plasmon resonance (SPR) approach. TTR bound to lipid bilayers through both high- and low-affinity interactions. Increasing the mole fraction of cholesterol in the bilayer led to an increase in the amount of high-affinity binding of an amyloidogenic mutant (L55P) TTR. In addition, a greater amount of L55P TTR bound with high affinity to membranes made from anionic phospholipids, phosphatidylglycerol (PG) and phosphatidylserine (PS), than to membranes made from zwitterionic phospholipid phosphatidylcholine (PC). The anionic phospholipids (PS and PG) promoted the aggregation of L55P TTR by accelerating the nucleation phase of aggregation, whereas the zwitterionic phospholipid PC had little effect. These results suggest that cholesterol and anionic phospholipids may be important for TTR aggregation and TTR-induced cytotoxicity.

Item Type: Article
Keywords: Transthyretin (TTR); Cholesterol; Phospholipid; Aggregation; Amyloid; Binding
Journal or Publication Title: Biochimica et Biophysica Acta - Biomembranes
Page Range: pp. 198-205
ISSN: 0005-2736
Identification Number - DOI: 10.1016/j.bbamem.2007.09.018
Additional Information: The definitive version is available at http://www.sciencedirect.com
Date Deposited: 30 Sep 2008 02:38
Last Modified: 18 Nov 2014 03:50
URI: http://eprints.utas.edu.au/id/eprint/7674
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