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Acta Crystallogr D Biol Crystallogr. 2014 Sep;70(Pt 9):2277-85. doi: 10.1107/S1399004714012267. Epub 2014 Aug 23.

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

Author information

1
Inflammation Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.
2
Biomolecular Interactions Centre and School of Biological Sciences, University of Canterbury, Private Bag 4800, Christchurch 8020, New Zealand.
3
Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria 3010, Australia.

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.

KEYWORDS:

GP130; JAK; STAT3; cytokine; interleukin

PMID:
25195742
DOI:
10.1107/S1399004714012267
[Indexed for MEDLINE]

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