title: Interaction of an esophageal MEG protein from schistosomes with a human S100 protein involved in inflammatory response.
abstract: 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.
authors.affiliation: Instituto de Física de São Carlos, Universidade de São Paulo, São Carlos, Brazil.
authors.forename: Débora
authors.initials: D
authors.lastname: Orcia
authors.affiliation: Instituto de Física de São Carlos, Universidade de São Paulo, São Carlos, Brazil.
authors.forename: Ana Eliza
authors.initials: AE
authors.lastname: Zeraik
authors.affiliation: Instituto de Física de São Carlos, Universidade de São Paulo, São Carlos, Brazil.
authors.forename: José L S
authors.initials: JLS
authors.lastname: Lopes
authors.affiliation: Instituto de Física de São Carlos, Universidade de São Paulo, São Carlos, Brazil.
authors.forename: Joci N A
authors.initials: JNA
authors.lastname: Macedo
authors.affiliation: Instituto de Física de São Carlos, Universidade de São Paulo, São Carlos, Brazil.
authors.forename: Clarissa Romano Dos
authors.initials: CRD
authors.lastname: Santos
authors.affiliation: Núcleo de Enteroparasitas, Centro de Parasitologia e Micologia, Instituto Adolfo Lutz, São Paulo, Brazil.
authors.forename: Katia C
authors.initials: KC
authors.lastname: Oliveira
authors.affiliation: Instituto de Química, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Leticia
authors.initials: L
authors.lastname: Anderson
authors.affiliation: Institute of Structural and Molecular Biology, Birkbeck College, University of London, London, U.K.
authors.forename: B A
authors.initials: BA
authors.lastname: Wallace
authors.affiliation: Instituto de Química, Universidade de São Paulo, São Paulo, Brazil; Instituto Butantan, São Paulo, SP, Brazil.
authors.forename: Sergio
authors.initials: S
authors.lastname: Verjovski-Almeida
authors.affiliation: Instituto de Física de São Carlos, Universidade de São Paulo, São Carlos, Brazil.
authors.forename: Ana P U
authors.initials: APU
authors.lastname: Araujo
authors.affiliation: Instituto de Física de São Carlos, Universidade de São Paulo, São Carlos, Brazil. Electronic address: rdemarco@ifsc.usp.br.
authors.forename: Ricardo
authors.initials: R
authors.lastname: DeMarco
mesh_terms: D017398:Alternative Splicing / Q000235:genetics; D000818:Animals; D002942:Circular Dichroism; D006224:Cricetinae; D004591:Electrophoresis, Polyacrylamide Gel; D004947:Esophagus / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D015800:Protozoan Proteins / Q000378:metabolism*; D009418:S100 Proteins / Q000378:metabolism*; D012550:Schistosoma mansoni / Q000378:metabolism*; D020349:Surface Plasmon Resonance; D020798:Two-Hybrid System Techniques
chemical_list: D015800:Protozoan Proteins; D009418:S100 Proteins
keywords: Intrinsically disordered proteins; Micro-exon gene; Protein-protein interaction; Synchrotron radiation circular dichroism spectroscopy