PMID- 15193916 OWN - NLM STAT- MEDLINE DCOM- 20040729 LR - 20071114 IS - 0042-6822 (Print) IS - 0042-6822 (Linking) VI - 323 IP - 2 DP - 2004 Jun 1 TI - Identification of residues in an orthopoxvirus interleukin-18 binding protein involved in ligand binding and species specificity. PG - 197-207 AB - 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. FAU - Esteban, David J AU - Esteban DJ AD - Department of Molecular Microbiology and Immunology, St. Louis University Health Sciences Center, St. Louis, MO 63104, USA. FAU - Buller, R Mark L AU - Buller RM LA - eng GR - U01 48653-04/PHS HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Virology JT - Virology JID - 0110674 RN - 0 (Glycoproteins) RN - 0 (Intercellular Signaling Peptides and Proteins) RN - 0 (Interleukin-18) RN - 0 (Ligands) RN - 0 (interleukin-18 binding protein) SB - IM MH - Amino Acid Sequence MH - Animals MH - Cell Line MH - Ectromelia virus/*pathogenicity MH - Glycoproteins/*chemistry/metabolism MH - Humans MH - Intercellular Signaling Peptides and Proteins MH - Interleukin-18/*metabolism MH - Ligands MH - Mice MH - Molecular Sequence Data MH - Mutagenesis, Site-Directed MH - Point Mutation MH - Protein Binding MH - Species Specificity MH - Surface Plasmon Resonance EDAT- 2004/06/15 05:00 MHDA- 2004/07/30 05:00 CRDT- 2004/06/15 05:00 PHST- 2003/11/03 00:00 [received] PHST- 2003/12/16 00:00 [revised] PHST- 2004/02/27 00:00 [accepted] PHST- 2004/06/15 05:00 [pubmed] PHST- 2004/07/30 05:00 [medline] PHST- 2004/06/15 05:00 [entrez] AID - S0042682204001631 [pii] AID - 10.1016/j.virol.2004.02.027 [doi] PST - ppublish SO - Virology. 2004 Jun 1;323(2):197-207. doi: 10.1016/j.virol.2004.02.027.