The role of arginine residues in interleukin 1 receptor binding.
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.
Nanduri
V B
VB
Department of Protein Biochemistry, Roche Research Center, Hoffmann-La Roche Inc., Nutley, NJ 07110-1199.
Hulmes
J D
JD
Pan
Y C
YC
Kilian
P L
PL
Stern
A S
AS
D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine / Q000737:chemistry; D003461:Crystallography; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000737:chemistry* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry; D010658:Phenylglyoxal / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D011971:Receptors, Immunologic / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins
D007375:Interleukin-1; D010446:Peptide Fragments; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D001120:Arginine; D010658:Phenylglyoxal