Protein Toxins That Utilize Gangliosides as Host Receptors

Prog Mol Biol Transl Sci. 2018;156:325-354. doi: 10.1016/bs.pmbts.2017.11.010. Epub 2018 Mar 17.


Subsets of protein toxins utilize gangliosides as host receptors. Gangliosides are preferred receptors due to their extracellular localization on the eukaryotic cell and due to their essential nature in host physiology. Glycosphingolipids, including gangliosides, are mediators of signal transduction within and between eukaryotic cells. Protein toxins possess AB structure-function organization, where the A domain encodes a catalytic function for the posttranslational modification of a host macromolecule, including proteins and nucleic acids, and a B domain, which encodes host receptor recognition, including proteins and glycosphingolipids, alone or in combination. Protein toxins use similar strategies to bind glycans by pockets and loops, generally employing hydrogen bonding and aromatic stacking to stabilize interactions with sugars. In some cases, glycan binding facilitates uptake, while in other cases, cross-linking or a second receptor is necessary to stimulate entry. The affinity that protein toxins have for host glycans is necessary for tissue targeting, but not always sufficient to cause disease. In addition to affinity for binding the glycan, the lipid moiety also plays an important role in productive uptake and tissue tropism. Upon endocytosis, the protein toxin must escape to another intracellular compartment or into cytosol to modify a host substrate, modulating host signaling, often resulting in cytotoxic or apoptotic events in the cell, and a unique morbidity for the organism. The study of protein toxins that utilize gangliosides as host receptors has illuminated numerous eukaryotic cellular processes, identified the basis for developing interventions to prevent disease through vaccines and control bacterial diseases through therapies. In addition, subsets of these protein toxins have been utilized as therapeutic agents to treat numerous human inflictions.

Keywords: endocytosis; gangliosides; protein structure; receptors; toxins.

Publication types

  • Review

MeSH terms

  • Animals
  • Binding Sites
  • Biological Transport
  • Cell Membrane / chemistry
  • Cell Membrane / metabolism*
  • Endocytosis*
  • Gangliosides / chemistry
  • Gangliosides / metabolism*
  • Host-Pathogen Interactions*
  • Humans
  • Receptors, Cell Surface / chemistry
  • Receptors, Cell Surface / metabolism*
  • Toxins, Biological / metabolism*


  • Gangliosides
  • Receptors, Cell Surface
  • Toxins, Biological