Abstract
The ubiquitination and deubiquitination of proteins can alter diverse cellular processes, such as proteolysis, trafficking, subcellular localisation, DNA repair, apoptosis and signal transduction. Deubiquitinating enzymes (DUBs) are responsible for removing ubiquitin from their target proteins. Previous reports have shown the presence of two subfamilies of DUBs in Schistosoma mansoni: Ub carboxyl-terminal hydrolase (UCH) and Ub-specific protease (USP). In this study, we analysed the ovarian tumour (OTU) and Machado-Joseph disease protein domain (MJD) proteases found in the Schistosoma mansoni genome database. An in silico analysis identified two different MJD subfamily members, SmAtaxin-3 and SmJosephin, and five distinct OTU proteases, SmOTU1, SmOTU3, SmOTU5a, SmOTU6b and SmOtubain. The phylogenetic analysis showed the evolutionary conservation of these proteins. Furthermore, the 3D structures confirmed the similarity of these proteins with human proteins. In addition, we performed quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and observed distinct expression profiles for all of the investigated transcripts between the cercariae, schistosomula and adult worm stages. Taken together, our data suggest that MJD and OTU subfamily members contribute to regulating the activity of the Ub-proteasome system during the life cycle of this parasite.
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Acknowledgments
The authors thank the following transcriptome initiatives: the São Paulo Transcriptome Consortium, the Minas Gerais Genome Network and the Wellcome Trust Genome Initiative (UK). This work was supported by the following Brazilian research agencies: Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG, CBB - APQ-02101-11), Núcleo de Bioinformática da Universidade Federal de Ouro Preto (NuBio UFOP) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).
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Figure S1
Model of the predicted tertiary structures based on template proteins deposited in theSWISS-MODEL server(Biasiniet al. 2014). The structures were visualized using CCP4mg in cartoon format.A) SmAtaxin, B) SmJosephin, C) SmOtub, D) SmOTU1, E) SmOTU3, F) SmOTU5a, and G) SmOTU6b (GIF 102 kb)
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Pereira, R.V., de Souza Gomes, M., Costa, M.P. et al. MJD and OTU deubiquitinating enzymes in Schistosoma mansoni . Parasitol Res 114, 2835–2843 (2015). https://doi.org/10.1007/s00436-015-4484-1
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DOI: https://doi.org/10.1007/s00436-015-4484-1