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

Marina Cardó-Vila, Amado J. Zurita, Ricardo J. Giordano, Jessica Sun, Roberto Rangel, Liliana Guzman-Rojas, Cristiane D. Anobom, Ana P. Valente, Fábio C.L. Almeida, Johanna Lahdenranta, Mikhail G. Kolonin, Wadih Arap, Renata Pasqualini

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

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-11Rα 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-11Rα has been proposed as a target in human cancer, our results provide clues for the rational design of targeted drugs.

Original languageEnglish (US)
Article numbere3452
JournalPloS one
Volume3
Issue number10
DOIs
StatePublished - 2008
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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