Differential sensitivity to Arg side chain modification of IL-1 beta binding to type I and type II receptors

• Published in: Agents and Actions Vol. 41; no. 1-2; pp. 105 - 107
• Main Authors: Tömösközi, Z, Bugovics, G, Koncz, S, Arányi, P
• Format: Journal Article
• Language: English
• Published: Switzerland 01-03-1994
• Subjects: Arginine - chemistry; Arginine - metabolism; Binding Sites; Cloning, Molecular; Humans; Interleukin-1 - chemistry; Interleukin-1 - metabolism; Macrophages - metabolism; Radioligand Assay; Receptors, Interleukin-1 - metabolism; Recombinant Proteins - metabolism
• ISSN: 0065-4299; 1420-908X
• DOI: 10.1007/BF01986407

The central role of interleukin-1 (IL-1) in several disease processes, including fever and inflammation, makes the characterization of ligand-receptor interaction of prime importance. The role of arginine (Arg) side chains of hr-IL-1 beta in receptor recognition was studied by the modification of Arg residues with the specific reagent 1,2-cyclohexanedione. It was found that chemical modification of Arg residues decreased the binding potential of IL-1 beta to type I receptor dramatically (by 230-fold) while the affinity to type II receptor was reduced only moderately (by 10-fold), with an insignificant reduction of the dissociation rate. These studies suggest that intact Arg side chains of IL-1 beta may be necessary for high affinity binding to type I IL-1 receptor, but have less importance for the interaction of IL-1 beta with type II IL-1 receptor. This observation may be useful in the study of type II IL-1 receptor-mediated biological responses and design of receptor-subtype specific ligands as well.