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

Autor(es):Mostrar menos -

Orcia, Debora ; Zeraik, Ana Eliza ; Lopes, Jose L. S. ; Macedo, Joci N. A. ; dos Santos, Clarissa Romano ; Oliveira, Katia C. ; Anderson, Leticia ; Wallace, B. A. ; Verjovski-Almeida, Sergio ; Araujo, Ana P. U. ; DeMarco, Ricardo

• Tipo de documento: Artigo Científico
• Fonte: BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS; v. 1861, n. 1, p. 8-pg., 2017-01-01.

Resumo

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. (C) 2016 Elsevier B.V. All rights reserved. (AU)

• Processo FAPESP: 12/07288-7 - Estudo da estrutura, imunorreatividade e parceiros proteicos de proteínas codificadas por genes de micro-exons de Schistosoma mansoni
• Beneficiário: Débora Orcia
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 13/20715-4 - Estudo da correlação entre a dinâmica de septinas e a homeostase de Ca2+ em células musculares de Schistosoma mansoni
• Beneficiário: Ana Eliza Zeraik
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 14/09361-9 - Estudo dos genes de micro-exon (MEGs) do parasita humano Schistosoma mansoni e da interação de seus produtos protéicos com células humanas
• Beneficiário: Ricardo de Marco
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 12/09186-7 - Estudo dos genes de micro-exon (MEGs) do parasita humano Schistosoma mansoni e seus produtos protéicos
• Beneficiário: Ricardo de Marco
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 10/20290-5 - Estudos estruturais de complexos de septinas humanas
• Beneficiário: Joci Neuby Alves Macedo
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado