title: Leucine-58 in the putative 5th helical region of human interleukin (IL)-6 is important for activation of the IL-6 signal transducer, gp130.
abstract: A model of the tertiary structure of human IL-6, derived from the crystal-structure of granulocyte-colony stimulating factor, reveals a 5th helical region in the loop between the first and second alpha-helix. To investigate the importance of this region for biological activity of IL-6, residues Glu-52, Ser-53, Ser-54, Lys-55, Glu-56, Leu-58, and Glu-60 were individually replaced by alanine. IL-6.Leu-58Ala displayed a 5-fold reduced biological activity on the IL-6 responsive human cell lines XG-1 and A375. This reduction in bioactivity was shown to be due to a decreased capacity of the mutant protein to trigger IL-6 receptor-alpha-chain-dependent binding to the IL-6 signal transducer, gp130.
authors.affiliation: Department of Autoimmune Diseases, University of Amsterdam, The Netherlands.
authors.forename: F D
authors.initials: FD
authors.lastname: de Hon
authors.forename: H K
authors.initials: HK
authors.lastname: Klaasse Bos
authors.forename: S B
authors.initials: SB
authors.lastname: Ebeling
authors.forename: J
authors.initials: J
authors.lastname: Grötzinger
authors.forename: G
authors.initials: G
authors.lastname: Kurapkat
authors.forename: S
authors.initials: S
authors.lastname: Rose-John
authors.forename: L A
authors.initials: LA
authors.lastname: Aarden
authors.forename: J P
authors.initials: JP
authors.lastname: Brakenhoff
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD; D001483:Base Sequence; D001667:Binding, Competitive; D002455:Cell Division; D050822:Cytokine Receptor gp130; D006801:Humans; D006825:Hybridomas; D015850:Interleukin-6 / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D007930:Leucine / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D018123:Receptors, Interleukin / Q000378:metabolism; D019947:Receptors, Interleukin-6; D016415:Sequence Alignment; D015398:Signal Transduction / Q000502:physiology*; D014407:Tumor Cells, Cultured
chemical_list: D015703:Antigens, CD; C494199:IL6ST protein, human; C494200:Il6st protein, mouse; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D018123:Receptors, Interleukin; D019947:Receptors, Interleukin-6; D050822:Cytokine Receptor gp130; D007930:Leucine