Document Detail


N-terminal horseshoe conformation of DCC is functionally required for axon guidance and might be shared by other neural receptors.
MedLine Citation:
PMID:  23038776     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 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.
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; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2012-10-04
Journal Detail:
Title:  Journal of cell science     Volume:  126     ISSN:  1477-9137     ISO Abbreviation:  J. Cell. Sci.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-03-21     Completed Date:  2013-09-11     Revised Date:  2014-01-09    
Medline Journal Info:
Nlm Unique ID:  0052457     Medline TA:  J Cell Sci     Country:  England    
Other Details:
Languages:  eng     Pagination:  186-95     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Axons
Cells, Cultured
Chromatography, Gel
Crystallography, X-Ray
Embryo, Mammalian / cytology
Immunohistochemistry
Immunoprecipitation
Mice
Mice, Knockout
Molecular Weight
Protein Structure, Tertiary
Receptors, Cell Surface / chemistry*,  metabolism*
Sensory Receptor Cells / chemistry,  metabolism*
Tumor Suppressor Proteins / chemistry*,  metabolism*
Grant Support
ID/Acronym/Agency:
CA107193/CA/NCI NIH HHS; HL48675/HL/NHLBI NIH HHS; RR-15301/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Dcc protein, rat; 0/Receptors, Cell Surface; 0/Tumor Suppressor Proteins
Comments/Corrections

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