Deleted in colorectal cancer. Chain: a. Fragment: unp residues 39-421. Synonym: deleted in colorectal carcinoma, isoform cra_a. Engineered: yes
Source:
Rattus norvegicus. Rat. Organism_taxid: 10116. Gene: dcc, rcg_46581. Expressed in: trichoplusia ni. Expression_system_taxid: 7111.
Resolution:
2.40Å
R-factor:
0.211
R-free:
0.231
Authors:
Q.Chen,J.-H.Liu,J.-H.Wang
Key ref:
Q.Chen
et al.
(2013).
N-terminal horseshoe conformation of DCC is functionally required for axon guidance and might be shared by other neural receptors.
J Cell Sci,
126,
186-195.
PubMed id: 23038776
DOI: 10.1242/jcs.111278
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.