The objective of this proposal is to determine the high resolution X-ray crystal structure of human granulocyte-macrophage colony-stimulating factor (GM-CSF). This protein growth factor is required for the proliferation of certain types of white blood cells (granulocytes and macrophages) from their progenitor cells in the bone marrow, as well as for promoting the survival and stimulating the physiological activities of these short-lived cells. The therapeutic use of GM-CSF produced by recombinant DNA techniques holds enormous promise for the treatment of a variety of immunosuppressive conditions. For example, GM-CSF administration can reverse the reduced white cell levels caused by AIDS, the treatment of cancer by chemotherapy and radiation therapy (thereby extending the potency of such treatments), and severe burns. GM-CSF may also be used to stimulate the immune system during severe infection and possibly to promote the tumoricidal action of white cells against cancer. We have crystallized a physiologically active recombinant human GM-CSF in a form suitable for high resolution X-ray diffraction analysis and intend to determine the crystal structure of this 128 amino acid residue protein by known crystallographic techniques. The results of this study should facilitate the development of therapeutically improved variants of GM-CSF by genetic engineering techniques.
| Bucy, R P; Chen, C L; Cooper, M D (1990) Development of cytoplasmic CD3+/T cell receptor-negative cells in the peripheral lymphoid tissues of chickens. Eur J Immunol 20:1345-50 |
