title: The structure of human interleukin-11 reveals receptor-binding site features and structural differences from interleukin-6.
abstract: Interleukin (IL)-11 is a multifunctional member of the IL-6 family of cytokines. Recombinant human IL-11 is administered as a standard clinical treatment for chemotherapy-induced thrombocytopaenia. Recently, a new role for IL-11 signalling as a potent driver of gastrointestinal cancers has been identified, and it has been demonstrated to be a novel therapeutic target for these diseases. Here, the crystal structure of human IL-11 is reported and the structural resolution of residues previously identified as important for IL-11 activity is presented. While IL-11 is thought to signal via a complex analogous to that of IL-6, comparisons show important differences between the two cytokines and it is suggested that IL-11 engages GP130 differently to IL-6. In addition to providing a structural platform for further study of IL-11, these data offer insight into the binding interactions of IL-11 with each of its receptors and the structural mechanisms underlying agonist and antagonist variants of the protein.
authors.affiliation: Inflammation Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.
authors.forename: Tracy L
authors.initials: TL
authors.lastname: Putoczki
authors.affiliation: Biomolecular Interactions Centre and School of Biological Sciences, University of Canterbury, Private Bag 4800, Christchurch 8020, New Zealand.
authors.forename: Renwick C J
authors.initials: RC
authors.lastname: Dobson
authors.affiliation: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Michael D W
authors.initials: MD
authors.lastname: Griffin
mesh_terms: D018360:Crystallography, X-Ray; D006801:Humans; D017370:Interleukin-11 / Q000737:chemistry* / Q000378:metabolism; D015850:Interleukin-6 / Q000737:chemistry*; D008958:Models, Molecular; D011487:Protein Conformation; D053702:Receptors, Interleukin-11 / Q000378:metabolism*; D014461:Ultracentrifugation
chemical_list: D017370:Interleukin-11; D015850:Interleukin-6; D053702:Receptors, Interleukin-11
keywords: GP130; JAK; STAT3; cytokine; interleukin