1w8a | pdb_00001w8a
Third LRR domain of Drosophila Slit
Structural highlights
Function[SLIT_DROME] A short-range repellent, controlling axon crossing of the midline and a long-range chemorepellent, controlling mesoderm migration and patterning away from the midline. May interact with extracellular matrix molecules. Repulsive ligand for the guidance receptor roundabout (robo) and prevents inappropriate midline crossing by Robo-expressing axons.[1] [2] [3] [4] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedRecognition of the large secreted protein Slit by receptors of the Robo family provides fundamental signals in axon guidance and other developmental processes. In Drosophila, Slit-Robo signalling regulates midline crossing and the lateral position of longitudinal axon tracts. We report the functional dissection of Drosophila Slit, using structure analysis, site-directed mutagenesis and in vitro assays. The N-terminal region of Slit consists of a tandem array of four independently folded leucine-rich repeat (LRR) domains, connected by disulphide-tethered linkers. All three Drosophila Robos were found to compete for a single highly conserved site on the concave face of the second LRR domain of Slit. We also found that this domain is sufficient for biological activity in a chemotaxis assay. Other Slit activities may require Slit dimerisation mediated by the fourth LRR domain. Our results show that a small portion of Slit is able to induce Robo signalling and indicate that the distinct functions of Drosophila Robos are encoded in their divergent cytosolic domains. Binding site for Robo receptors revealed by dissection of the leucine-rich repeat region of Slit.,Howitt JA, Clout NJ, Hohenester E EMBO J. 2004 Nov 10;23(22):4406-12. Epub 2004 Oct 21. PMID:15496984[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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