1W8A

Third LRR domain of Drosophila Slit

Summary for 1W8A

• Entry DOI: 10.2210/pdb1w8a/pdb
• Related: 1OZN
• Descriptor: SLIT PROTEIN (2 entities in total)
• Functional Keywords: signaling protein, secreted protein, axon guidance, leucine-rich repeat glycoprotein, egf-like domain, signal protein
• Biological source: DROSOPHILA MELANOGASTER (Fruit fly)
• Cellular location: Secreted : P24014
• Total number of polymer chains: 1
• Total formula weight: 21313.31

Authors

Howitt, J.A.,Clout, N.J.,Hohenester, E. (deposition date: 2004-09-17, release date: 2004-10-25, Last modification date: 2024-11-20)

Primary citation

Howitt, J.A.,Clout, N.J.,Hohenester, E.
Binding Site for Robo Receptors Revealed by Dissection of the Leucine-Rich Repeat Region of Slit.
Embo J., 23:4406-, 2004

PubMed Abstract: Recognition 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.

PubMed: 15496984
DOI: 10.1038/SJ.EMBOJ.7600446

Experimental method

X-RAY DIFFRACTION (2.8 Å)