N-terminal horseshoe conformation of DCC is functionally required for axon guidance and might be shared by other neural receptors.

ABSTRACT: 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 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

SUBMITTER: Chen Q 

PROVIDER: S-EPMC3603515 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature