title: Identification of regions in interleukin-1 alpha important for activity.
abstract: Saturation mutagenesis of the mature human interleukin-1 alpha (IL-1 alpha) gene has been performed. Following expression in Escherichia coli, the biological and receptor binding activities of the mutant proteins were examined. Most of the molecule could be altered with little effect on either function. More than 3,500 mutants were examined, and only 23 unique amino acid sequences were identified which resulted in an altered ratio of biological to binding activity when compared with wild-type IL-1 alpha. These proteins possessed mutations at 38 of the 159 amino acid residues in IL-1 alpha. Random mutagenesis at several of these positions identified further substitutions that affected activity. Examination of a model for IL-1 alpha localized most of the residues which altered activity along one face of the molecule. This region appears to be distinct from areas of IL-1 which have been postulated to make contact with IL-1 receptor.
authors.affiliation: Immunex Research and Development Corporation, Seattle, Washington 98101.
authors.forename: R B
authors.initials: RB
authors.lastname: Gayle
authors.forename: K
authors.initials: K
authors.lastname: Poindexter
authors.forename: D
authors.initials: D
authors.lastname: Cosman
authors.forename: S K
authors.initials: SK
authors.lastname: Dower
authors.forename: S
authors.initials: S
authors.lastname: Gillis
authors.forename: T
authors.initials: T
authors.lastname: Hopp
authors.forename: R
authors.initials: R
authors.lastname: Jerzy
authors.forename: S
authors.initials: S
authors.lastname: Kronheim
authors.forename: V
authors.initials: V
authors.lastname: Lum
authors.forename: A
authors.initials: A
authors.lastname: Lewis
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D004247:DNA; D004926:Escherichia coli; D006801:Humans; D007375:Interleukin-1 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid
chemical_list: D007375:Interleukin-1; D004247:DNA