The role of arginine residues in interleukin 1 receptor binding.

V B Nanduri, J D Hulmes, Y C Pan, P L Kilian, A S Stern

Department of Protein Biochemistry, Roche Research Center, Hoffmann-La Roche Inc., Nutley, NJ 07110-1199.

Biochimica et biophysica acta 1991 Dec 11

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Interleukin 1 (IL-1) is a family of polypeptide cytokines that plays an essential role in modulating immune and inflammatory responses. IL-1 activity is mediated by either of two distinct proteins, IL-1 alpha or IL-1 beta, both of which bind to the same receptor found on T-lymphocytes, fibroblasts and endothelial cells (Type 1 receptor). The effect of specific chemical modification of recombinant IL-1 alpha and IL-1 beta on receptor binding was examined. Modification of the proteins with phenylglyoxal, an arginine-specific reagent, resulted in the loss of Type 1 IL-1 receptor binding activity. The stoichiometry of this modification revealed that a single arginine in either IL-1 alpha or IL-1 beta is responsible for the loss of activity. Cyanogen bromide cleavage of phenylglyoxal modified IL-1 alpha and IL-1 beta, followed by sequencing of the peptides, revealed that arginine-12 in IL-1 alpha and arginine-4 in IL-1 beta, which occupy the same topology in the respective crystallographic structures, are the target of phenylglyoxal. These results suggest that an arginine residue plays an important role in ligand-receptor interaction.

Citation

V B Nanduri, J D Hulmes, Y C Pan, P L Kilian, A S Stern. The role of arginine residues in interleukin 1 receptor binding. Biochimica et biophysica acta. 1991 Dec 11;1118(1):25-35