STRUCTURE DETERMINATION OF A COMPLEX OF CYTOKINE RECEPTORS AND LIGAND

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We are interested in the structural basis of signalling of cytokine receptor systems involving GM-CSF and the interleukins IL-3 and IL-5. Signalling involves the specific binding of a cytokine ligand to a membrane bound a receptor, followed by a second binding of this binary complex with another membrane bound receptor (b). This latter binding event stimulates cross membrane signalling and associated JAK/STAT kinase cascades inside the cell. These receptors are potential drug targets for the treatment of allergic diseases such as asthma. The x-ray structure of the b-common receptor revealed an unusual interlocking dimer (Carr et al., 2001, Cell, 104, 291-300) suggestive of a novel mechanism in this system. We have managed to produce crystals from a complex containing the extracellular components of all three signalling molecules (cytokine, a receptor and b receptor). It is these crystals we wish to use for a structure determination.