Poster Presentation The 43rd Lorne Conference on Protein Structure and Function 2018

Towards the first high resolution structure of Interleukin-11Rα (#158)

Kaheina Aizel 1 , Courtney Zlatic 2 , Riley Metcalfe 2 , Tracy Putoczki 1 , Michael Griffin 2
  1. The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia
  2. Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria, Australia

Interleukin-11 (IL-11) is a multifunctional cytokine, which binds to specific cell surface receptors and initiates immune responses, epithelial cell proliferation, differentiation and apoptosis. Recently, it has been revealed that increased expression of IL-11 is associated with numerous diseases including cancer. IL-11 utilises the transmembrane β-subunit signal transducing receptor, GP130, which interacts with IL-11 and its α-subunit receptor (IL-11Ra). Of the three components of the IL-11 signalling complex, only GP130 and IL-11 have high-resolution crystal structures. Currently, the only structural data available for the entire signaling complex is derived from cryo-electron microscopy of the mouse IL-11/IL-11Rα/GP130 hexameric complex. The 30 Å resolution electron density map calculated from these images was interpreted using the crystal structure of the IL-6 signalling complex. Since no crystallographic structure for IL-11Rα is available our aim was to generate a high-resolution structure in order to begin to interrogate how the IL-11 signalling complex assembles and functions. To achieve this, we have undertaken crystal trials for the extracellular regions of human IL-11Rα and GP130, and have previously published the structure of IL-11. Small angle X-ray scattering analysis of the different components of the signalling complex together has also been performed. Our results will provide a platform for the design of therapeutics targeting this pathway.