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    Functional conservation of an ancestral Pellino protein in helminth species


    Cluxton, Christopher and Caffrey, Brian E. and Kinsella, Gemma K. and Moynagh, Paul N. and Fares, Mario A. and Fallon, Padraic G. (2015) Functional conservation of an ancestral Pellino protein in helminth species. Scientific Reports, 5 (11687). ISSN 2045-2322

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    Abstract

    The immune system of H. sapiens has innate signaling pathways that arose in ancestral species. This is exemplified by the discovery of the Toll-like receptor (TLR) pathway using free-living model organisms such as Drosophila melanogaster. The TLR pathway is ubiquitous and controls sensitivity to pathogen-associated molecular patterns (PAMPs) in eukaryotes. There is, however, a marked absence of this pathway from the plathyhelminthes, with the exception of the Pellino protein family, which is present in a number of species from this phylum. Helminth Pellino proteins are conserved having high similarity, both at the sequence and predicted structural protein level, with that of human Pellino proteins. Pellino from a model helminth, Schistosoma mansoni Pellino (SmPellino), was shown to bind and poly-ubiquitinate human IRAK-1, displaying E3 ligase activity consistent with its human counterparts. When transfected into human cells SmPellino is functional, interacting with signaling proteins and modulating mammalian signaling pathways. Strict conservation of a protein family in species lacking its niche signalling pathway is rare and provides a platform to examine the ancestral functions of Pellino proteins that may translate into novel mechanisms of immune regulation in humans.

    Item Type: Article
    Additional Information: How to cite this article: Cluxton, C. D. et al. Functional conservation of an ancestral Pellino protein in helminth species. Sci. Rep. 5, 11687; doi: 10.1038/srep11687 (2015). This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
    Keywords: Functional conservation; ancestral Pellino protein; helminth species;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 11030
    Identification Number: https://doi.org/10.1038/srep11687
    Depositing User: Professor Paul Moynagh
    Date Deposited: 10 Sep 2019 14:35
    Journal or Publication Title: Scientific Reports
    Publisher: Nature Publishing Group
    Refereed: Yes
    Funders: Health Research Board (HRB), Science Foundation Ireland (SFI), National Children’s Research Centre
    URI:

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