Differential sensitivity to Arg side chain modification of IL-1 beta binding to type I and type II receptors.
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.
Tömösközi
Z
Z
Institute for Drug Research, Budapest, Hungary.
Bugovics
G
G
Koncz
S
S
Arányi
P
P
D001120:Arginine / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D003001:Cloning, Molecular; D006801:Humans; D007375:Interleukin-1 / Q000737:chemistry / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D011869:Radioligand Assay; D017472:Receptors, Interleukin-1 / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism
D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D001120:Arginine