N-terminal horseshoe conformation of DCC is functionally required for axon guidance and might be shared by other neural receptors.
J Cell Sci
; 126(Pt 1): 186-95, 2013 Jan 01.
Article
en En
| MEDLINE
| ID: mdl-23038776
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Células Receptoras Sensoriales
/
Receptores de Superficie Celular
/
Proteínas Supresoras de Tumor
Tipo de estudio:
Guideline
Límite:
Animals
Idioma:
En
Revista:
J Cell Sci
Año:
2013
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Reino Unido