title: Structure-function analysis of human IL-1 alpha: identification of residues required for binding to the human type I IL-1 receptor.
abstract: Using oligonucleotide-directed mutagenesis, the binding site on human interleukin-1 alpha (IL-1 alpha) for the human type I IL-1 receptor (IL-1R) has been analyzed. Substitution of seven amino acids (Arg12, Ile14, Asp60, Asp61, Ile64, Lys96 and Trp109) resulted in a significant loss of binding to the receptor. Based on crystallographic information, the side chains of these residues are clustered in one region of IL-1 alpha and exposed on the surface of the protein. Five of the residues in the IL-1 alpha binding site align with the binding residues previously determined in human IL-1 beta, demonstrating that the type I IL-1R recognizes homologous regions in both ligands. Unexpectedly, only three of the aligned residues are identical between IL-1 alpha and IL-1 beta. These observations suggest that the composition of contact residues in the binding site is unique for each ligand-receptor complex in the IL-1 system.
authors.affiliation: Department of Inflammation/Autoimmune Diseases, Roche Research Center, Hoffmann-La Roche Inc., Nutley, NJ 07110.
authors.forename: E
authors.initials: E
authors.lastname: Labriola-Tompkins
authors.forename: C
authors.initials: C
authors.lastname: Chandran
authors.forename: T A
authors.initials: TA
authors.lastname: Varnell
authors.forename: V S
authors.initials: VS
authors.lastname: Madison
authors.forename: G
authors.initials: G
authors.lastname: Ju
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000235:genetics; D001667:Binding, Competitive; D016466:CHO Cells; D006224:Cricetinae; D004252:DNA Mutational Analysis; D000939:Epitopes / Q000235:genetics; D006801:Humans; D007375:Interleukin-1 / Q000031:analogs & derivatives / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D016297:Mutagenesis, Site-Directed; D017472:Receptors, Interleukin-1 / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000939:Epitopes; D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins