Membrane fusion mediated by non-covalent binding of re-engineered cholera toxin assemblies to glycolipids

16 July 2021, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


Membrane fusion is essential for the transport of macromolecules and viruses across membranes. While glycan-binding proteins (lectins) often initiate cellular adhesion, subsequent fusion events require additional protein machinery. No mechanism for membrane fusion arising from simply a protein binding to membrane glycolipids has been described thus far. Herein we report that a biotinylated protein derived from cholera toxin, becomes a fusogenic lectin upon crosslinking with streptavidin. This novel reengineered protein brings about hemifusion and fusion of vesicles as demonstrated by mixing of fluorescently labelled lipids between vesicles as well as content mixing of liposomes filled with fluorescently labelled dextran. Exclusion of the complex at vesicle-vesicle interfaces could also be observed indicating the formation of hemifusion diaphragms. We propose that negative membrane curvature, caused by binding of the cholera toxin to the membrane surface, induces formation of a fusion stalk as a result of high bending energies building up between multiple inverted membrane dimples aligned on opposing membranes at the vesicle-vesicle interface. Discovery of this fusogenic lectin complex demonstrates that new emergent properties can arise from simple changes in protein architecture and provides insights towards new mechanisms of lipid-driven fusion


membrane fusion
bacterial toxin

Supplementary materials

Supplementary Information
supplementary figures, supplementary video captions, supplementary experimental methods

Supplementary weblinks


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