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

Miao, Haofei; Jia, Yingying; Xie, Sichun; Wang, Xin; Zhao, Jinling; Chu, Youjun; Zhou, Zhilei; Shi, Zhubing; Song, Xiaomin; Li, Lin

doi:10.1074/jbc.m114.591636

Cited by 17 publications

(20 citation statements)

References 34 publications

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“…The C1q domain of Cbln1 preserves the secondary structure topology of the most similar C1q domains found in Caprin-2 and C1QL proteins 1 to 3, while having unique features (Kakegawa et al, 2015; Miao et al, 2014; Ressl et al, 2015). The “top half” of the C1q domain in proximity to the CRN can be closely superimposed with the C1q crystal structures of Caprin-2 and C1QL proteins, while the bottom half of Cbln1 C1q domain shows a large divergence from its homologs (Figures 3F, S2A–C).…”

Section: Resultsmentioning

confidence: 95%

“…This crystal yielded a 1.8 Å-resolution dataset in the hexagonal P 6 space group. We determined the structure of Cbln1 using the monomer for the C1q-like structure of human Caprin-2 (PDB: 4OUM) (Miao et al, 2014) as a molecular replacement model, which has 39% sequence identity to the C1q-like domain of Cbln1. The crystallographic data and refinement statistics are in Table 1.…”

Section: Resultsmentioning

confidence: 99%

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Conformational Plasticity in the Transsynaptic Neurexin-Cerebellin-Glutamate Receptor Adhesion Complex

et al. 2016

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Synaptic specificity is a defining property of neural networks. In the cerebellum, synapses between parallel fiber neurons and Purkinje cells are specified by the simultaneous interactions of secreted protein Cerebellin with presynaptic Neurexin and postsynaptic delta-type Glutamate receptors (GluD). Here, we determined the crystal structures of the trimeric C1q-like domain of rat Cerebellin-1, and the first complete ectodomain of a GluD, rat GluD2. Cerebellin binds to the LNS6 domain of α- and β-Neurexin-1 through a high-affinity interaction that involves its highly flexible N-terminal domain. In contrast, we show that the interaction of Cerebellin with isolated GluD2 ectodomain is low affinity, which is not simply an outcome of lost avidity when compared to binding with a tetrameric full-length receptor. Rather, high-affinity capture of Cerebellin by post-synaptic terminals is likely controlled by long-distance regulation within this trans-synaptic complex. Altogether, our results suggest unusual conformational flexibility within all components of the complex.

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Section: Resultsmentioning

confidence: 95%

Section: Resultsmentioning

confidence: 99%

Conformational Plasticity in the Transsynaptic Neurexin-Cerebellin-Glutamate Receptor Adhesion Complex

et al. 2016

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“…The sequences of HR1 and HR2 do not conform to any consensus sequence for known protein domains suggestive of functions. Caprin-2 has an identifiable structural domain at its C-terminus (CRD; C1q-related domain) which is homologous to the globular head domain of the complement protein C1q (Shapiro & Scherer, 1998;Gaboriaud et al, 2003;Garlatti et al, 2010;Venkatraman Girija et al, 2013;Miao et al, 2014). Caprin-1 and Caprin-2 also contain RGG boxes and RG-rich sequences characteristic of RNA-binding proteins near the C-terminal region of HR2 (Fig.…”

Section: Introductionmentioning

confidence: 99%

Bacterial expression and preliminary crystallographic studies of a 149-residue fragment of human Caprin-1

Zhu

Huang

et al. 2015

Acta Cryst Sect F

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Caprin-1 is an RNA-binding protein which plays critical roles in several important biological processes, including cellular proliferation, the interferonmediated antiviral innate immune response, the maintenance of synaptic plasticity and the formation of RNA stress granules. Caprin-1 has been implicated in the pathogenesis of several human diseases, including osteosarcoma, breast cancer, viral infections, hearing loss and neurodegenerative disorders. Despite the emerging biological and physiopathological significance of Caprin-1, no structural information is available for this protein. Moreover, Caprin-1 does not have sequence similarity to any other protein with a known structure. It is therefore expected that structural studies will play a particularly crucial role in revealing the functional mechanisms of Caprin-1. Here, a protein fragment of human Caprin-1 consisting of residues 112-260 was expressed, purified and crystallized. Native and Se-SAD data sets were collected to resolutions to 2.05 and 2.65 Å , respectively, in different space groups.

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“…Also, the structure of human C1qgD complexed with CRP and IgG were modeled . Recent years, the crystal structures of human and zebrafish Caprin‐2 C1q‐related domain (Cap2_CRD) was determined by Miao et al . However, no data have been found to focus on the structure of fish complement system.…”

Section: Introductionmentioning

confidence: 99%

“…5,[14][15][16][17] Also, the structure of human C1qgD complexed with CRP and IgG were modeled. 5,6,18 Recent years, the crystal structures of human and zebrafish Caprin-2 C1q-related domain (Cap2_CRD) was determined by Miao et al 19 However, no data have been found to focus on the structure of fish complement system. Zebrafish (Danio rerio) C1q genes have conserved chromosomal characteristics compared to other species, such as human and mouse.…”

Section: Introductionmentioning

confidence: 99%

Crystal structure of zebrafish complement 1qA globular domain

et al. 2016

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C1q contains three globular domains (C1qgD) that are the key functional component of the classical complement system. C1qgD can interact with important immune molecules, including IgG and C-reactive protein (CRP) to form defense systems to protect animals. Here, the first nonmammalian structure, zebrafish C1qA globular domain (Dare-C1qAgD) was solved. Although the overall architecture of Dare-C1qAgD is similar to human C1qA, residues involved in C1qBgD, C1qCgD, and CRP binding are somewhat different while residues involved in IgG binding are not present in zebrafish. The structure gives insight into how human and fish C1qA evolved from an ancestral protein.

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

Cited by 17 publications

References 34 publications

Conformational Plasticity in the Transsynaptic Neurexin-Cerebellin-Glutamate Receptor Adhesion Complex

Conformational Plasticity in the Transsynaptic Neurexin-Cerebellin-Glutamate Receptor Adhesion Complex

Bacterial expression and preliminary crystallographic studies of a 149-residue fragment of human Caprin-1

Crystal structure of zebrafish complement 1qA globular domain

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