Leucine-58 in the putative 5th helical region of human interleukin (IL)-6 is important for activation of the IL-6 signal transducer, gp130.
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.
de Hon
F D
FD
Department of Autoimmune Diseases, University of Amsterdam, The Netherlands.
Klaasse Bos
H K
HK
Ebeling
S B
SB
Grötzinger
J
J
Kurapkat
G
G
Rose-John
S
S
Aarden
L A
LA
Brakenhoff
J P
JP
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
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