Multi-scale molecular dynamics study of cholera pentamer binding to a GM1-phospholipid membrane

• Interaction of Cholera ‘B’ Pentamer with an asymmetrical GM1-DPPC bilayer is studied.
• The bound configuration consists of only three ‘B’ chains tethered to the membrane.
• Toxin binding causes membrane thinning, tail disorder and increase in area per lipid.
• Effects of binding extend across both leaflets of the membrane.

The AB5 type toxin produced by the Vibrio cholerae bacterium is the causative agent of the cholera disease. The cholera toxin (CT) has been shown to bind specifically to GM1 glycolipids on the membrane surface. This binding of CT to the membrane is the initial step in its endocytosis and has been postulated to cause significant disruption to the membrane structure. In this work, we have carried out a combination of coarse-grain and atomistic simulations to study the binding of CT to a membrane modelled as an asymmetrical GM1-DPPC bilayer. Simulation results indicate that the toxin binds to the membrane through only three of its five B subunits, in effect resulting in a tilted bound configuration. Additionally, the binding of the CT can increase the area per lipid of GM1 leaflet, which in turn can cause the membrane regions interacting with the bound subunits to experience significant bilayer thinning and lipid tail disorder across both the leaflets.

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