Multimerization and interaction of Toll and Spatzle in Drosophila
UMass Chan Affiliations
Department of Biochemistry & Molecular PharmacologyProgram in Molecular Medicine
Document Type
Journal ArticlePublication Date
2004-06-16Keywords
AnimalsAnimals, Genetically Modified
Antifungal Agents
Cloning, Molecular
Cysteine
Disulfides
Drosophila
Drosophila Proteins
Kinetics
Macromolecular Substances
Mutagenesis, Site-Directed
Receptors, Cell Surface
Recombinant Proteins
Sequence Deletion
Toll-Like Receptors
Life Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
The Toll family of receptors is required for innate immune response to pathogen-associated molecules, but the mechanism of signaling is not entirely clear. In Drosophila the prototypic Toll regulates both embryonic development and adult immune response. We demonstrate here that the host protein Spatzle can function as a ligand for Toll because Spatzle forms a complex with Toll in transgenic fly extracts and stimulates the expression of a Toll-dependent immunity gene, drosomycin, in adult flies. We also show that constitutively active mutants of Toll form multimers that contain intermolecular disulfide linkages. These disulfide linkages are critical for the activity of one of these mutant receptors, indicating that multimerization is essential for the constitutive activity. Furthermore, systematic mutational analysis revealed that a conserved cysteine-containing motif, different from the cysteines used for the intermolecular disulfide linkages, serves as a self-inhibitory module of Toll. Deleting or mutating this cysteine-containing motif leads to constitutive activity. This motif is located just outside the transmembrane domain and may provide a structural hindrance for multimerization and activation of Toll. Together, our results suggest that multimerization may be a regulated, essential step for Toll-receptor activation.Source
Proc Natl Acad Sci U S A. 2004 Jun 22;101(25):9369-74. Epub 2004 Jun 14. Link to article on publisher's site
DOI
10.1073/pnas.0307062101Permanent Link to this Item
http://hdl.handle.net/20.500.14038/38930PubMed ID
15197269Related Resources
ae974a485f413a2113503eed53cd6c53
10.1073/pnas.0307062101