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An ELISA Based Binding and Competition Method to Rapidly Determine Ligand-receptor Interactions
Published on: March 14, 2016
Diversifying selection and functional analysis of interleukin-4 suggests antagonism-driven evolution at
Madoka Koyanagi1, Julie A Kerns, Linda Chung
1Department of Immunology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.
BMC Evolutionary Biology
|July 24, 2010
Summary
Parasitic helminths may antagonize Interleukin-4 (IL4) to spread. Studies show IL4 evolved to avoid pathogen antagonism while maintaining receptor binding and signaling functions.
Area of Science:
- Evolutionary biology
- Immunology
- Molecular biology
Background:
- Interleukin-4 (IL4) is a key cytokine for host defense against parasitic helminths.
- Helminths may have evolved strategies to counteract IL4 to enhance their transmission.
Purpose of the Study:
- To investigate the evolutionary adaptations of mammalian Interleukin-4 (IL4).
- To determine if IL4 has evolved to evade antagonism by pathogens while preserving its function.
Main Methods:
- Analysis of mammalian IL4 evolution.
- Functional assessment of IL4 allotypes in Mus musculus subspecies.
- Examination of IL4 binding to IL4 receptor alpha (IL4Ralpha) and signaling through Type I and Type II receptors.
Main Results:
- Evidence of diversifying selection at 15 residues in IL4, clustered in receptor-binding epitopes.
- Intra-species variation in IL4 allotypes did not affect IL4 binding to IL4Ralpha or Type I receptor signaling.
- Positively selected sites in IL4 are functionally important for host-pathogen interactions.
Conclusions:
- IL4 evolution appears shaped by pathogen antagonism, leading to adaptations that avoid evasion by parasites.
- IL4 retains its capacity to bind cognate receptors and signal biological responses.
- Evolutionary conflicts at protein-protein interaction interfaces can drive the emergence of receptor-binding epitopes that buffer variation.
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