Abstract

Prof. Angel Lopez, Head of Division of Human Immunology, Institute of Medical and Veterinary Science, Australia.



Cytokine receptors are the means by which normal and malignant hemopoietic cells recognize soluble signals in the microenvironment. In binding their cognate cytokine or growth factor, cytokine receptors assemble on the cell surface in a configuration that allows their activation, recruitment of signalling molecules and triggering of multiple biological responses. Defining how polypeptide receptor subunits interact with each other and how they assemble into an active complex is therefore critical to understand how cytokine receptors signal. In collaboration with Professor Michael Parker's group (St Vincent's Institute of Medical Research, Melbourne), we have now determined the structure of the human GM-CSF ternary complex assembled in solution. This shows a novel and unexpected type of cytokine receptor assembly which mutagenesis and functional experiments reveal is the basic GM-CSF receptor active unit. The exogenous manipulation of the critical sites of receptor assembly may provide new opportunities to interfere with cytokine receptor function in certain diseases.

Host: Dr. Vinay Tergaonkar