Document Detail


N-terminal horseshoe conformation of DCC is functionally required for axon guidance and may be shared by other neural receptors.
MedLine Citation:
PMID:  23038776     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
DCC (Deleted in Colorectal Cancer) is a receptor for 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. Here, we present 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, which nearly all function in the nervous system. The N-terminal horseshoe appears to be evolutionally selected as a platform for neural receptors.
Authors:
Qiang Chen; Xiaqin Sun; Xiao-Hong Zhou; Jin-Huan Liu; Jane Wu; Yan Zhang; Jia-Huai Wang
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-4
Journal Detail:
Title:  Journal of cell science     Volume:  -     ISSN:  1477-9137     ISO Abbreviation:  J. Cell. Sci.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-5     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0052457     Medline TA:  J Cell Sci     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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