A ligand peptide motif selected from a cancer patient is a receptor-interacting site within human interleukin-11

PLoS One. 2008;3(10):e3452. doi: 10.1371/journal.pone.0003452. Epub 2008 Oct 20.


Interleukin-11 (IL-11) is a pleiotropic cytokine approved by the FDA against chemotherapy-induced thrombocytopenia. From a combinatorial selection in a cancer patient, we isolated an IL-11-like peptide mapping to domain I of the IL-11 (sequence CGRRAGGSC). Although this motif has ligand attributes, it is not within the previously characterized interacting sites. Here we design and validate in-tandem binding assays, site-directed mutagenesis and NMR spectroscopy to show (i) the peptide mimics a receptor-binding site within IL-11, (ii) the binding of CGRRAGGSC to the IL-11R alpha is functionally relevant, (iii) Arg4 and Ser8 are the key residues mediating the interaction, and (iv) the IL-11-like motif induces cell proliferation through STAT3 activation. These structural and functional results uncover an as yet unrecognized receptor-binding site in human IL-11. Given that IL-11R alpha has been proposed as a target in human cancer, our results provide clues for the rational design of targeted drugs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Binding Sites / genetics
  • Cell Proliferation
  • Humans
  • Interleukin-11 / genetics
  • Interleukin-11 / metabolism*
  • Interleukin-11 Receptor alpha Subunit / genetics
  • Interleukin-11 Receptor alpha Subunit / metabolism*
  • Ligands
  • Molecular Mimicry
  • Mutagenesis, Site-Directed
  • Neoplasms / chemistry*
  • Peptide Fragments / isolation & purification
  • Peptide Fragments / metabolism*
  • Protein Binding
  • STAT3 Transcription Factor / metabolism


  • Interleukin-11
  • Interleukin-11 Receptor alpha Subunit
  • Ligands
  • Peptide Fragments
  • STAT3 Transcription Factor