@article {117,
	title = {Binding of the Drosophila cytokine Sp{\"a}tzle to Toll is direct and establishes signaling.},
	journal = {Nature immunology},
	volume = {4},
	year = {2003},
	month = {2003 Aug},
	pages = {794-800},
	abstract = {The extracellular protein Sp{\"a}tzle is required for activation of the Toll signaling pathway in the embryonic development and innate immune defense of Drosophila. Sp{\"a}tzle is synthesized as a pro-protein and is processed to a functional form by a serine protease. We show here that the mature form of Sp{\"a}tzle triggers a Toll-dependent immune response after injection into the hemolymph of flies. Sp{\"a}tzle specifically bound to Drosophila cells and to Cos-7 cells expressing Toll. Furthermore, in vitro experiments showed that the mature form of Sp{\"a}tzle bound to the Toll ectodomain with high affinity and with a stoichiometry of one Sp{\"a}tzle dimer to two receptors. The Sp{\"a}tzle pro-protein was inactive in all these assays, indicating that the pro-domain sequence, which is natively unstructured, acts to prevent interaction of the cytokine and its receptor Toll. These results show that, in contrast to the human Toll-like receptors, Drosophila Toll requires only an endogenous protein ligand for activation and signaling.},
	keywords = {Animals, Drosophila, Drosophila Proteins, Insect Proteins, Protein Binding, Protein Structure, Tertiary, Receptors, Cell Surface, Signal Transduction, Toll-Like Receptors},
	issn = {1529-2908},
	doi = {10.1038/ni955},
	author = {Weber, Alexander N R and Tauszig-Delamasure, Servane and Hoffmann, Jules A and Leli{\`e}vre, Eric and Gascan, Hugues and Ray, Keith P and Morse, Mary A and Imler, Jean-Luc and Gay, Nicholas J}
}
