A Conserved Structural Motif Mediates Retrograde Trafficking of Shiga Toxin Types 1 and 2

Traffic. 2015 Dec;16(12):1270-87. doi: 10.1111/tra.12338. Epub 2015 Nov 2.


Shiga toxin-producing Escherichia coli (STEC) produce two types of Shiga toxin (STx): STx1 and STx2. The toxin A-subunits block protein synthesis, while the B-subunits mediate retrograde trafficking. STEC infections do not have definitive treatments, and there is growing interest in generating toxin transport inhibitors for therapy. However, a comprehensive understanding of the mechanisms of toxin trafficking is essential for drug development. While STx2 is more toxic in vivo, prior studies focused on STx1 B-subunit (STx1B) trafficking. Here, we show that, compared with STx1B, trafficking of the B-subunit of STx2 (STx2B) to the Golgi occurs with slower kinetics. Despite this difference, similar to STx1B, endosome-to-Golgi transport of STx2B does not involve transit through degradative late endosomes and is dependent on dynamin II, epsinR, retromer and syntaxin5. Importantly, additional experiments show that a surface-exposed loop in STx2B (β4-β5 loop) is required for its endosome-to-Golgi trafficking. We previously demonstrated that residues in the corresponding β4-β5 loop of STx1B are required for interaction with GPP130, the STx1B-specific endosomal receptor, and for endosome-to-Golgi transport. Overall, STx1B and STx2B share a common pathway and use a similar structural motif to traffic to the Golgi, suggesting that the underlying mechanisms of endosomal sorting may be evolutionarily conserved.

Keywords: Golgi; bacterial toxin; endosome; protein motif; trafficking.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Motifs
  • Consensus Sequence
  • Conserved Sequence
  • Endosomes / metabolism
  • Evolution, Molecular
  • Galactosyltransferases / genetics
  • Golgi Apparatus / metabolism
  • HeLa Cells
  • Humans
  • Kinetics
  • Protein Binding
  • Protein Subunits
  • Protein Transport
  • Shiga Toxin 1 / chemistry
  • Shiga Toxin 1 / genetics
  • Shiga Toxin 1 / metabolism*
  • Shiga Toxin 2 / chemistry
  • Shiga Toxin 2 / genetics
  • Shiga Toxin 2 / metabolism*
  • Shiga-Toxigenic Escherichia coli / metabolism*
  • Vesicular Transport Proteins / metabolism


  • GOLIM4 protein, human
  • Protein Subunits
  • Shiga Toxin 1
  • Shiga Toxin 2
  • Vesicular Transport Proteins
  • shiga toxin 2 B subunit
  • Galactosyltransferases
  • UDP-galactose-lactosylceramide alpha 1-4-galactosyltransferase