Deleted 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 Nterminal 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. © 2013.
CITATION STYLE
Chen, Q., Sun, X., Zhou, X. hong, Liu, J. huan, Wu, J., Zhang, Y., & Wang, J. huai. (2013). N-terminal horseshoe conformation of DCC is functionally required for axon guidance and might be shared by other neural receptors. Journal of Cell Science, 126(1), 186–195. https://doi.org/10.1242/jcs.111278
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