PUBLICATION
Structural Insights into the C1q Domain of Caprin-2 in Canonical Wnt Signaling
- Authors
- Miao, H., Jia, Y., Xie, S., Wang, X., Zhao, J., Chu, Y., Zhou, Z., Shi, Z., Song, X., Li, L.
- ID
- ZDB-PUB-141022-6
- Date
- 2014
- Source
- The Journal of biological chemistry 289(49): 34104-13 (Journal)
- Registered Authors
- Keywords
- C1q, Caprin-2, Wnt pathway, Wnt signaling, calcium-binding protein, crystal structure, mutagenesis
- MeSH Terms
-
- Animals
- Calcium/chemistry*
- Calcium/metabolism
- Cell Cycle Proteins/chemistry*
- Cell Cycle Proteins/genetics
- Cell Cycle Proteins/metabolism
- Complement C1q/chemistry*
- Complement C1q/metabolism
- Crystallography, X-Ray
- Escherichia coli/genetics
- Escherichia coli/metabolism
- Gene Expression Regulation
- HEK293 Cells
- Humans
- Models, Molecular
- Mutation
- Protein Multimerization
- Protein Structure, Secondary
- Protein Structure, Tertiary
- Recombinant Proteins/chemistry
- Recombinant Proteins/genetics
- Recombinant Proteins/metabolism
- Wnt Signaling Pathway
- Zebrafish
- PubMed
- 25331957 Full text @ J. Biol. Chem.
Citation
Miao, H., Jia, Y., Xie, S., Wang, X., Zhao, J., Chu, Y., Zhou, Z., Shi, Z., Song, X., Li, L. (2014) Structural Insights into the C1q Domain of Caprin-2 in Canonical Wnt Signaling. The Journal of biological chemistry. 289(49):34104-13.
Abstract
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; while 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping