Peer-Reviewed Journal Details
Mandatory Fields
Cluxton, CD;Caffrey, BE;Kinsella, GK;Moynagh, PN;Fares, MA;Fallon, PG
2015
June
Scientific Reports
Functional conservation of an ancestral Pellino protein in helminth species
Published
2 ()
Optional Fields
TOLL-LIKE RECEPTORS SCHISTOSOMA-MANSONI INNATE IMMUNITY MOLECULAR-DYNAMICS ACTIVATION FAMILY EXPRESSION KINASES IRAK1 POLYUBIQUITINATION
5
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.
LONDON
2045-2322
10.1038/srep11687
Grant Details