4OUS

Crystal structure of zebrafish Caprin-2 C1q domain

Summary for 4OUS

• Entry DOI: 10.2210/pdb4ous/pdb
• Related: 4OUL 4OUM
• Descriptor: Caprin-2, CALCIUM ION (3 entities in total)
• Functional Keywords: c1q domain, wnt signaling, signaling protein
• Biological source: Danio rerio (leopard danio,zebra danio,zebra fish)
• Cellular location: Cytoplasm : Q5RJ80
• Total number of polymer chains: 1
• Total formula weight: 16120.19

Authors

Song, X.,Li, L. (deposition date: 2014-02-18, release date: 2014-10-29, Last modification date: 2023-11-08)

Primary citation

Miao, H.,Jia, Y.,Xie, S.,Wang, X.,Zhao, J.,Chu, Y.,Zhou, Z.,Shi, Z.,Song, X.,Li, L.
Structural insights into the C1q domain of Caprin-2 in canonical Wnt signaling
J.Biol.Chem., 289:34104-34113, 2014

PubMed 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, 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.

PubMed: 25331957
DOI: 10.1074/jbc.M114.591636

Experimental method

X-RAY DIFFRACTION (1.05 Å)