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Structure of DCC, a netrin-1 receptor
Structural highlights
FunctionDCC_RAT Receptor for netrin required for axon guidance. Mediates axon attraction of neuronal growth cones in the developing nervous system upon ligand binding. Its association with UNC5 proteins may trigger signaling for axon repulsion. It also acts as a dependence receptor required for apoptosis induction when not associated with netrin ligand. Implicated as a tumor suppressor gene (By similarity).[1] Publication Abstract from PubMedDeleted in colorectal cancer (DCC) is a receptor for the axon guidance cues netrin-1 and draxin. The interactions between these guidance cues and DCC play a key role in the development of the nervous system. In the present study, we reveal the crystal structure of the N-terminal four Ig-like domains of DCC. The molecule folds into a horseshoe-like configuration. We demonstrate that this horseshoe conformation of DCC is required for guidance-cue-mediated axonal attraction. Structure-based mutations that disrupt the DCC horseshoe indeed impair its function. A comparison of the DCC horseshoe with previously described horseshoe structures has revealed striking conserved structural features and important sequence signatures. Using these signatures, a genome-wide search allows us to predict the N-terminal horseshoe arrangement in a number of other cell surface receptors, nearly all of which function in the nervous system. The N-terminal horseshoe appears to be evolutionally selected as a platform for neural receptors. N-terminal horseshoe conformation of DCC is functionally required for axon guidance and might be shared by other neural receptors.,Chen Q, Sun X, Zhou XH, Liu JH, Wu J, Zhang Y, Wang JH J Cell Sci. 2013 Jan 1;126(Pt 1):186-95. doi: 10.1242/jcs.111278. Epub 2012 Oct, 4. PMID:23038776[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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