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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.

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

Author information

1
Instituto de Física de São Carlos, Universidade de São Paulo, São Carlos, Brazil.
2
Núcleo de Enteroparasitas, Centro de Parasitologia e Micologia, Instituto Adolfo Lutz, São Paulo, Brazil.
3
Instituto de Química, Universidade de São Paulo, São Paulo, Brazil.
4
Institute of Structural and Molecular Biology, Birkbeck College, University of London, London, U.K.
5
Instituto de Química, Universidade de São Paulo, São Paulo, Brazil; Instituto Butantan, São Paulo, SP, Brazil.
6
Instituto de Física de São Carlos, Universidade de São Paulo, São Carlos, Brazil. Electronic address: rdemarco@ifsc.usp.br.

Abstract

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

PMID:
27639541
DOI:
10.1016/j.bbagen.2016.09.015
[Indexed for MEDLINE]

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