| Structural highlights
5zo2 is a 3 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , |
| Related: | 1z9m, 5zo1 |
| Gene: | Cadm4, Igsf4c, Necl4, Tsll2 (LK3 transgenic mice), Cadm3, Igsf4b, Necl1, Syncam3, Tsll1 (LK3 transgenic mice) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[CADM4_MOUSE] Involved in the cell-cell adhesion. Has calcium- and magnesium-independent cell-cell adhesion activity. May have tumor-suppressor activity.[1] [CADM3_MOUSE] Involved in the cell-cell adhesion. Has both calcium-independent homophilic cell-cell adhesion activity and calcium-independent heterophilic cell-cell adhesion activity with IGSF4, NECTIN1 and NECTIN3. Interaction with EPB41L1 may regulate structure or function of cell-cell junctions.[2] [3]
Publication Abstract from PubMed
Nectin-like (Necl) molecules are Ca(2+)-independent Ig-like transmembrane cell adhesion molecules that participate in junctions between different cell types. The specific cell-cell adhesions mediated by Necl proteins are important in neural development and have been implicated in neurodegenerative diseases. Here, we present the crystal structure of the mouse Necl-4 full ectodomain and the structure of the heterophilic Necl ectodomain complex formed by the mNecl-4 and mNecl-1 ectodomains. We demonstrate that, while the ectodomain of mNecl-4 is monomeric, it forms a stable heterodimer with Ig1 of mNecl-1, with an affinity significantly higher than that observed for self-dimerization of the mNecl-1 ectodomain. We validated our structural characterizations by performing a surface plasmon resonance assay and an Fc fusion protein binding assay in mouse primary dorsal root ganglia neurites and Schwann cells and identified a selection of residues important for heterophilic interactions. Finally, we proposed a model of Necl binding specificity that involves an induced-fit conformational change at the dimerization interface.
Structure of the heterophilic interaction between the nectin-like 4 and nectin-like 1 molecules.,Liu X, An T, Li D, Fan Z, Xiang P, Li C, Ju W, Li J, Hu G, Qin B, Yin B, Wojdyla JA, Wang M, Yuan J, Qiang B, Shu P, Cui S, Peng X Proc Natl Acad Sci U S A. 2019 Feb 5;116(6):2068-2077. doi:, 10.1073/pnas.1810969116. Epub 2019 Jan 23. PMID:30674679[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Fukami T, Satoh H, Williams YN, Masuda M, Fukuhara H, Maruyama T, Yageta M, Kuramochi M, Takamoto S, Murakami Y. Isolation of the mouse Tsll1 and Tsll2 genes, orthologues of the human TSLC1-like genes 1 and 2 (TSLL1 and TSLL2). Gene. 2003 Dec 24;323:11-8. PMID:14659875
- ↑ Kakunaga S, Ikeda W, Itoh S, Deguchi-Tawarada M, Ohtsuka T, Mizoguchi A, Takai Y. Nectin-like molecule-1/TSLL1/SynCAM3: a neural tissue-specific immunoglobulin-like cell-cell adhesion molecule localizing at non-junctional contact sites of presynaptic nerve terminals, axons and glia cell processes. J Cell Sci. 2005 Mar 15;118(Pt 6):1267-77. Epub 2005 Mar 1. PMID:15741237 doi:http://dx.doi.org/jcs.01656
- ↑ Zhou Y, Du G, Hu X, Yu S, Liu Y, Xu Y, Huang X, Liu J, Yin B, Fan M, Peng X, Qiang B, Yuan J. Nectin-like molecule 1 is a protein 4.1N associated protein and recruits protein 4.1N from cytoplasm to the plasma membrane. Biochim Biophys Acta. 2005 May 20;1669(2):142-54. Epub 2005 Feb 25. PMID:15893517 doi:http://dx.doi.org/S0005-2736(05)00028-3
- ↑ Liu X, An T, Li D, Fan Z, Xiang P, Li C, Ju W, Li J, Hu G, Qin B, Yin B, Wojdyla JA, Wang M, Yuan J, Qiang B, Shu P, Cui S, Peng X. Structure of the heterophilic interaction between the nectin-like 4 and nectin-like 1 molecules. Proc Natl Acad Sci U S A. 2019 Feb 5;116(6):2068-2077. doi:, 10.1073/pnas.1810969116. Epub 2019 Jan 23. PMID:30674679 doi:http://dx.doi.org/10.1073/pnas.1810969116
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