title: Functional conservation of an ancestral Pellino protein in helminth species.
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.
authors.affiliation: School of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Cluxton
authors.affiliation: Department of Genetics, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Brian E
authors.initials: BE
authors.lastname: Caffrey
authors.affiliation: Institute of Immunology, National University of Ireland Maynooth, County Kildare, Ireland.
authors.forename: Gemma K
authors.initials: GK
authors.lastname: Kinsella
authors.affiliation: Institute of Immunology, National University of Ireland Maynooth, County Kildare, Ireland.
authors.forename: Paul N
authors.initials: PN
authors.lastname: Moynagh
authors.affiliation: 1] Department of Genetics, Trinity College Dublin, Dublin 2, Ireland [2] Integrative Systems Biology Group, Instituto de Biología Molecular y Celular de Plantas (C.S.I.C-UPV).
authors.forename: Mario A
authors.initials: MA
authors.lastname: Fares
authors.affiliation: 1] School of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland [2] National Children's Research Centre, Our Lady's Children's Hospital, Dublin 8, Ireland.
authors.forename: Padraic G
authors.initials: PG
authors.lastname: Fallon
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D017124:Conserved Sequence; D015801:Helminth Proteins / Q000737:chemistry / Q000378:metabolism*; D006376:Helminths / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D012550:Schistosoma mansoni / Q000737:chemistry; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013045:Species Specificity; D051193:Toll-Like Receptors / Q000378:metabolism
chemical_list: D000596:Amino Acids; D015801:Helminth Proteins; D009687:Nuclear Proteins; D051193:Toll-Like Receptors