Structural Insights into the C1q Domain of Caprin-2 in Canonical Wnt Signaling

	Structural Insights into the C1q Domain of Caprin-2 in Canonical Wnt Signaling
	Miao, HF; Jia, YY; Xie, SC; Wang, X; Zhao, JF; Chu, YJ; Zhou, ZL; Shi, ZB; Song, XM; Li, L
刊名	JOURNAL OF BIOLOGICAL CHEMISTRY
	2014
卷号	289 期号:49 页码:34104-34113
关键词	Calcium-binding Protein Crystal Structure Mutagenesis Wnt Pathway Wnt Signaling C1q Caprin-2
通讯作者	Song, XM (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Mol Biol, Shanghai 200031, Peoples R China.,xmsong01@sibcb.ac.cn ; lli@sibs.ac.cn
英文摘要	Background: Caprin-2 is a newly identified regulator in canonical Wnt signaling. Results: Mutants targeting trimer contacts of Caprin-2 CRD rather than calcium-binding sites affect the function of Caprin-2 in canonical Wnt signaling. Conclusion: Caprin-2 CRD forms a flexible homotrimer mediated by calcium, and this trimeric assembly is required for the function of Caprin-2. Significance: This work facilitates our understanding of how Caprin-2 functions in canonical Wnt signaling. 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.
学科主题	Biochemistry & Molecular Biology
类目[WOS]	Biochemistry & Molecular Biology
关键词[WOS]	TUMOR-NECROSIS-FACTOR ; CRYSTAL-STRUCTURE ; RNA GRANULES ; PROTEIN ; RECOGNITION ; PHOSPHORYLATION ; FAMILY ; TRIMER ; TRANSLATION ; MOLECULE
收录类别	SCI
语种	英语
WOS记录号	WOS:000346077600035
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/274]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Miao, HF,Jia, YY,Xie, SC,et al. Structural Insights into the C1q Domain of Caprin-2 in Canonical Wnt Signaling[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2014,289(49):34104-34113.
APA	Miao, HF.,Jia, YY.,Xie, SC.,Wang, X.,Zhao, JF.,...&Li, L.(2014).Structural Insights into the C1q Domain of Caprin-2 in Canonical Wnt Signaling.JOURNAL OF BIOLOGICAL CHEMISTRY,289(49),34104-34113.
MLA	Miao, HF,et al."Structural Insights into the C1q Domain of Caprin-2 in Canonical Wnt Signaling".JOURNAL OF BIOLOGICAL CHEMISTRY 289.49(2014):34104-34113.