Leucine-58 in the putative 5th helical region of human interleukin (IL)-6 is important for activation of the IL-6 signal transducer, gp130

FEBS Lett. 1995 Aug 7;369(2-3):187-91. doi: 10.1016/0014-5793(95)00741-q.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, CD*
  • Base Sequence
  • Binding, Competitive
  • Cell Division
  • Cytokine Receptor gp130
  • Humans
  • Hybridomas
  • Interleukin-6 / chemistry
  • Interleukin-6 / genetics
  • Interleukin-6 / physiology*
  • Leucine / physiology*
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Receptors, Interleukin / metabolism
  • Receptors, Interleukin-6
  • Sequence Alignment
  • Signal Transduction / physiology*
  • Tumor Cells, Cultured

Substances

  • Antigens, CD
  • IL6ST protein, human
  • Il6st protein, mouse
  • Interleukin-6
  • Membrane Glycoproteins
  • Receptors, Interleukin
  • Receptors, Interleukin-6
  • Cytokine Receptor gp130
  • Leucine