| Structural highlights
Function
CADM4_MOUSE Involved in the cell-cell adhesion. Has calcium- and magnesium-independent cell-cell adhesion activity. May have tumor-suppressor activity.[1]
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[2]
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
- ↑ 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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