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

• Published in: Biochimica et biophysica acta. General subjects Vol. 1861; no. 1; pp. 3490 - 3497
• Main Authors: Orcia, Débora, Zeraik, Ana Eliza, Lopes, José L.S., Macedo, Joci N.A., Santos, Clarissa Romano dos, Oliveira, Katia C., Anderson, Leticia, Wallace, B.A., Verjovski-Almeida, Sergio, Araujo, Ana P.U., DeMarco, Ricardo
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.01.2017
• Subjects: Alternative Splicing - genetics; Animals; antigenic variation; cDNA libraries; Circular Dichroism; circular dichroism spectroscopy; complementary DNA; Cricetinae; Electrophoresis, Polyacrylamide Gel; Esophagus - metabolism; fluorescent dyes; Humans; inflammation; Inflammation - pathology; Intrinsically disordered proteins; Micro-exon gene; parasites; plasma cells; Protein Binding; Protein Structure, Secondary; Protein-protein interaction; proteins; Protozoan Proteins - metabolism; S100 Proteins - metabolism; Schistosoma mansoni; Schistosoma mansoni - metabolism; Surface Plasmon Resonance; Synchrotron radiation circular dichroism spectroscopy; Two-Hybrid System Techniques; Synchrotron radiation circular dichroism spectroscopy; Micro-exon gene; Protein-protein interaction; Intrinsically disordered proteins
• ISSN: 0304-4165; 1872-8006
• DOI: 10.1016/j.bbagen.2016.09.015

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. 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. 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. S100A9, a protein previously described to be involved in modulation of inflammatory response, was found to interact with sMEG-14. 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. •Interaction of a S. mansoni MEG and a human immune-regulatory protein is described.•Structural changes are detected when MEG-14 interacts with S100A9.•MEG-14 interacts with S100A8/A9 dimer with lower affinity than with S100A9 homodimer.•Human S100A9 specifically accumulates in the parasite esophagus when ingested.