Identification of residues in an orthopoxvirus interleukin-18 binding protein involved in ligand binding and species specificity.
Interleukin-18 (IL-18) is a critical cytokine in inflammation and adaptive immune responses. The IL-18 binding proteins (IL-18BP) are a family of proteins that bind to, and inhibit the activity of, IL-18. Using point mutagenesis, we analyzed the ectromelia virus IL-18BP to identify residues involved in binding. Because p13 can bind both human and murine IL-18, and because it is highly homologous to the variola virus IL-18BP, we set out to identify residues that may be involved in species specificity. Several of the mutations resulted in complete abrogation of binding affinity. Three (F49A, E77A, and E69A) significantly affected binding with both species of IL-18, but not to the same extent. Mutant H70A showed reduced affinity for human IL-18 while binding to murine IL-18 was not affected. This study demonstrated that interaction of IL-18 with p13 was similar to other IL-18BPs, however, novel species-specific interactions were identified.
Esteban
David J
DJ
Department of Molecular Microbiology and Immunology, St. Louis University Health Sciences Center, St. Louis, MO 63104, USA.
Buller
R Mark L
RM
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D004481:Ectromelia virus / Q000472:pathogenicity*; D006023:Glycoproteins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D020382:Interleukin-18 / Q000378:metabolism*; D008024:Ligands; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D017354:Point Mutation; D011485:Protein Binding; D013045:Species Specificity; D020349:Surface Plasmon Resonance
D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D020382:Interleukin-18; D008024:Ligands; C118370:interleukin-18 binding protein