Interaction of an esophageal MEG protein from schistosomes with a human S100 protein involved in inflammatory response

Biochim Biophys Acta Gen Subj. 2017 Jan;1861(1 Pt A):3490-3497. doi: 10.1016/j.bbagen.2016.09.015. Epub 2016 Sep 15.


Background: The Micro-Exon Gene-14 (MEG-14) displays a remarkable structure that allows the generation of antigenic variation in Schistosomes. Previous studies showed that the soluble portion of the MEG-14 protein displays features of an intrinsically disordered protein and is expressed exclusively in the parasite esophageal gland. These features indicated a potential for interaction with host proteins present in the plasma and cells from ingested blood.

Methods: A yeast two-hybrid experiment using as bait the soluble domain of Schistosoma mansoni MEG-14 (sMEG-14) against a human leukocyte cDNA library was performed. Pull-down and surface plasmon resonance (SPR) experiments were used to validate the interaction between sMEG-14 and human S100A9. Synchrotron radiation circular dichroism (SRCD) were used to detect structural changes upon interaction between sMEG-14 and human S100A9. Feeding of live parasites with S100A9 attached to a fluorophore allowed the tracking of the fate of this protein in the parasite digestive system.

Results: S100A9 interacted with sMEG-14 consistently in yeast two-hybrid assay, pull-down and SPR experiments. SRCD suggested that MEG-14 acquired a more regular structure as a result of the interaction with S100A9. Accumulation of recombinant S100A9 in the parasite's esophageal gland, when ingested by live worms suggests that such interaction may occur in vivo.

Conclusion: S100A9, a protein previously described to be involved in modulation of inflammatory response, was found to interact with sMEG-14.

General significance: Our results allow proposing a mechanism involving MEG-14 for the parasite to block inflammatory signaling, which would occur upon release of S100A9 when ingested blood cells are lysed.

Keywords: Intrinsically disordered proteins; Micro-exon gene; Protein-protein interaction; Synchrotron radiation circular dichroism spectroscopy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing / genetics
  • Animals
  • Circular Dichroism
  • Cricetinae
  • Electrophoresis, Polyacrylamide Gel
  • Esophagus / metabolism*
  • Humans
  • Inflammation / pathology*
  • Protein Binding
  • Protein Structure, Secondary
  • Protozoan Proteins / metabolism*
  • S100 Proteins / metabolism*
  • Schistosoma mansoni / metabolism*
  • Surface Plasmon Resonance
  • Two-Hybrid System Techniques


  • Protozoan Proteins
  • S100 Proteins