4OUM: Crystal Structure Of Human Caprin-2 C1q Domain

Previously, we have identified Caprin-2 as a new regulator in canonical Wnt signaling through a mechanism of facilitating LRP5/6 phosphorylation; moreover, we found that its C-terminal C1q-related domain (Cap2_CRD) is required for this process. Here, we determined the crystal structures of Cap2_CRD from human and zebrafish, which both associate as a homotrimer with calcium located at the symmetric center. Surprisingly, the calcium binding-deficient mutant exists as a more stable trimer than its wild-type counterpart. Further studies showed that this Caprin-2 mutant disabled in binding calcium maintains the activity of promoting LRP5/6 phosphorylation, whereas the mutations disrupting Cap2_CRD homotrimer did impair such activity. Together, our findings suggested that the C-terminal CRD domain of Caprin-2 forms a flexible homotrimer mediated by calcium and that such trimeric assembly is required for Caprin-2 to regulate canonical Wnt signaling.
PDB ID: 4OUMDownload
MMDB ID: 124324
PDB Deposition Date: 2014/2/18
Updated in MMDB: 2014/11
Experimental Method:
x-ray diffraction
Resolution: 1.49  Å
Source Organism:
Similar Structures:
Biological Unit for 4OUM: trimeric; determined by author and by software (PISA)
Molecular Components in 4OUM
Label Count Molecule
Proteins (3 molecules)
Caprin-2(Gene symbol: CAPRIN2)
Molecule annotation
Chemicals (9 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB