Structural and Functional Analysis of the GM-CSF:GM-CSF Receptor Alpha Chain Binary Complex — ASN Events

Structural and Functional Analysis of the GM-CSF:GM-CSF Receptor Alpha Chain Binary Complex (#203)

Mara Dottore 1 , Barbara J McClure 1 , Timothy R Hercus 1 , Sophie E Broughton 2 , Tracy L Nero 2 , Houng H Taing 1 , Michael W Parker 2 3 , Angel F Lopez 1
  1. Centre for Cancer Biology, Adelaide, SA, Australia
  2. Biota Structural Biology Laboratory, St. Vincent's Institute of Medical Research, Melbourne, Victoria, Australia
  3. Department of Biochemistry and Molecular Biology, Bio21 Molecular Science Institute, University of Melbourne, Melbourne, Victoria, Australia

Granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin-3 (IL-3) and interleukin-5 (IL-5) are important cytokines that play a significant role in cancer. They control the production and function of myeloid cells and dendritic cells, and are recognised as key players in clinically important immunopathological conditions such as rheumatoid arthritis and asthma.

All three cytokines signal through specific heterodimeric receptors consisting of a major binding alpha subunit that is ligand-specific and a signalling subunit, bc, that is shared by all receptors for all three cytokines. We have now used a combination of molecular biology, cell biology, biochemistry, crystallization and computer modelling to obtain 3D structures of the binary GM-CSF: GM-CSF receptor alpha chain complex based on X ray diffraction data collected to 2.8 Å resolution. This structure provides new insights into recognition and signalling by the bc class of cytokine receptors.