Phase Partitioning of GM1 and Its Bodipy-Labeled Analog Determine Their Different Binding to Cholera Toxin

Show full item record



Permalink

http://hdl.handle.net/10138/209213

Citation

Rissanen , S , Grzybek , M , Orlowski , A , Rog , T , Cramariuc , O , Levental , I , Eggeling , C , Sezgin , E & Vattulainen , I 2017 , ' Phase Partitioning of GM1 and Its Bodipy-Labeled Analog Determine Their Different Binding to Cholera Toxin ' , Frontiers in Physiology , vol. 8 , 252 . https://doi.org/10.3389/fphys.2017.00252

Title: Phase Partitioning of GM1 and Its Bodipy-Labeled Analog Determine Their Different Binding to Cholera Toxin
Author: Rissanen, Sami; Grzybek, Michal; Orlowski, Adam; Rog, Tomasz; Cramariuc, Oana; Levental, Ilya; Eggeling, Christian; Sezgin, Erdinc; Vattulainen, Ilpo
Contributor: University of Helsinki, Department of Physics
University of Helsinki, Department of Physics
Date: 2017-05-09
Language: eng
Number of pages: 7
Belongs to series: Frontiers in Physiology
ISSN: 1664-042X
URI: http://hdl.handle.net/10138/209213
Abstract: Driven by interactions between lipids and proteins, biological membranes display lateral heterogeneity that manifests itself in a mosaic of liquid-ordered (Lo) or raft, and liquid-disordered (Ld) or non-raft domains with a wide range of different properties and compositions. In giant plasma membrane vesicles and giant unilamellar vesicles, specific binding of Cholera Toxin (CTxB) to GM1 glycolipids is a commonly used strategy to label raft domains or Lo membrane environments. However, these studies often use acyl-chain labeled bodipy-GM1 (bdGM1), whose headgroup accessibility and membrane order or phase partitioning may differ from those of GM1, rendering the interpretation of CTxB binding data quite problematic. To unravel the molecular basis of CTxB binding to GM1 and bdGM1, we explored the partitioning and the headgroup presentation of these gangliosides in the Lo and Ld phases using atomistic molecular dynamics simulations complemented by CTxB binding experiments. The conformation of both GM1 and bdGM1 was shown to be largely similar in the Lo and Ld phases. However, bdGM1 showed reduction in receptor availability when reconstituted into synthetic bilayer mixtures, highlighting that membrane phase partitioning of the gangliosides plays a considerable role in CTxB binding. Our results suggest that the CTxB binding is predominately modulated by the partitioning of the receptor to an appropriate membrane phase. Further, given that the Lo and Ld partitioning of bdGM1 differs from those of GM1, usage of bdGM1 for studying GM1 behavior in cells can lead to invalid interpretation of experimental data.
Subject: GM1
ganglioside
cholera toxin
membrane domains
molecular dynamics simulations
model membranes
GALACTOSE-OXIDASE
RECEPTOR-ACTIVITY
MODEL MEMBRANES
CHOLESTEROL
GLYCOSPHINGOLIPIDS
BEHAVIOR
GLYCOLIPIDS
LIPOSOMES
EXPOSURE
1182 Biochemistry, cell and molecular biology
1184 Genetics, developmental biology, physiology
Rights:


Files in this item

Total number of downloads: Loading...

Files Size Format View
fphys_08_00252.pdf 3.405Mb PDF View/Open

This item appears in the following Collection(s)

Show full item record