Functional conservation of an ancestral Pellino protein in helminth species

Christopher D Cluxton, Brian E Caffrey, Gemma K Kinsella, Paul N Moynagh, Mario A Fares, Padraic G Fallon

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)
177 Downloads (Pure)

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.

Original languageEnglish
Article number11687
Number of pages11
JournalScientific Reports
Volume5
DOIs
Publication statusPublished - 29 Jun 2015

Keywords

  • Amino Acid Sequence
  • Amino Acids
  • Animals
  • Conserved Sequence
  • Helminth Proteins
  • Helminths
  • Humans
  • Molecular Sequence Data
  • Nuclear Proteins
  • Phylogeny
  • Protein Structure, Tertiary
  • Schistosoma mansoni
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Species Specificity
  • Toll-Like Receptors
  • Journal Article
  • Research Support, Non-U.S. Gov't

Fingerprint Dive into the research topics of 'Functional conservation of an ancestral Pellino protein in helminth species'. Together they form a unique fingerprint.

Cite this