The structure of human interleukin-11 reveals receptor-binding site features and structural differences from interleukin-6

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.