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

Citation

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

DOI: doi:10.1016/j.bbamem.2007.09.018

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 Details

Item Type:Refereed Article
Research Division:Biological Sciences
Research Group:Biochemistry and Cell Biology
Research Field:Cell Neurochemistry
Objective Division:Health
Objective Group:Specific Population Health (excl. Indigenous Health)
Objective Field:Health Related to Ageing
UTAS Author:Small, DH (Professor David Small)
ID Code:52822
Year Published:2008
Web of Science® Times Cited:20
Deposited By:Menzies Institute for Medical Research
Deposited On:2008-09-26
Last Modified:2009-04-25
Downloads:0

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