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Leucine‐58 in the putative 5th helical region of human interleukin (IL)‐6 is important for activation of the IL‐6 signal transducer, gp130
Author(s) -
de Hon Floris D.,
Bos Hanny Klaasse,
Ebeling Saskia B.,
Grötzinger Joachim,
Kurapkat Günther,
Rose-John Stefan,
Aarden Lucien A.,
Brakenhoff Just.P.J.
Publication year - 1995
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(95)00741-q
Subject(s) - glycoprotein 130 , mutant , alanine , chemistry , receptor , biological activity , interleukin 11 , biophysics , microbiology and biotechnology , biology , interleukin , amino acid , biochemistry , cytokine , signal transduction , immunology , in vitro , stat3 , gene
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 α‐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‐α‐chain‐dependent binding to the IL‐6 signal transducer, gp130.