A Ligand Peptide Motif Selected from a Cancer Patient Is a Receptor-Interacting Site within Human Interleukin-11

作者：Cardo Vila Marina^*; Zurita Amado J; Giordano Ricardo J; Sun Jessica; Rangel Roberto; Guzman Rojas Liliana; Anobom Cristiane D; Valente Ana P; Almeida Fabio C L; Lahdenranta Johanna; Kolonin Mikhail G; Arap Wadih; Pasqualini Renata

来源：PLos One, 2008, 3(10): e3452.

DOI：10.1371/journal.pone.0003452

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) Arg(4) and Ser(8) 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.

• 出版日期2008-10-20