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Issue 8, 2014
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Influence of Gb3 glycosphingolipids differing in their fatty acid chain on the phase behaviour of solid supported membranes: chemical syntheses and impact of Shiga toxin binding

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Abstract

The Shiga toxin B subunit (STxB), which is involved in cell membrane attachment and trafficking of Shiga holotoxin, binds specifically to the glycosphingolipid Gb3. In biological membranes, Gb3 glycosphingolipids differ in their fatty acid composition and there is strong evidence that the fatty acid alters the binding behaviour of STxB as well as the intracellular routing of the Shiga toxin/Gb3 complex. To analyse the binding of STxB to different Gb3s, we chemically synthesized saturated, unsaturated, α-hydroxylated Gb3s and a combination thereof, all based on a C24-fatty acid chain starting from monosaccharide building blocks, sphingosine and the respective fatty acids. These chemically well-defined Gb3s were inserted into solid supported phase-separated lipid bilayers composed of DOPC/sphingomyelin/cholesterol as a simple mimetic of the outer leaflet of animal cell membranes. By fluorescence- and atomic force microscopy the phase behaviour of the bilayer as well as the lateral organization of bound STxB were analysed. The fatty acid of Gb3 significantly alters the ratio between the ordered and disordered phase and induces a third intermediate phase in the presence of unsaturated Gb3. The lateral organization of STxB on the membranes varies significantly. While STxB attached to membranes with Gb3s with saturated fatty acids forms protein clusters, it is more homogeneously bound to membranes containing unsaturated Gb3s. Large interphase lipid redistribution is observed for α-hydroxylated Gb3 doped membranes. Our results clearly demonstrate that the fatty acid of Gb3 strongly influences the lateral organization of STxB on the membrane and impacts the overall membrane organization of phase-separated lipid membranes.

Graphical abstract: Influence of Gb3 glycosphingolipids differing in their fatty acid chain on the phase behaviour of solid supported membranes: chemical syntheses and impact of Shiga toxin binding

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Supplementary files

Article information


Submitted
05 May 2014
Accepted
13 May 2014
First published
15 May 2014

This article is Open Access
All publication charges for this article have been paid for by the Royal Society of Chemistry

Chem. Sci., 2014,5, 3104-3114
Article type
Edge Article

Influence of Gb3 glycosphingolipids differing in their fatty acid chain on the phase behaviour of solid supported membranes: chemical syntheses and impact of Shiga toxin binding

O. M. Schütte, A. Ries, A. Orth, L. J. Patalag, W. Römer, C. Steinem and D. B. Werz, Chem. Sci., 2014, 5, 3104
DOI: 10.1039/C4SC01290A

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