Mus musculus (house mouse)
The dynamic cellular and morphological changes during development of multicellular organisms are controlled by mechanisms of cell adhesion. One of the most important and ubiquitous adhesive interactions in both vertebrates and invertebrates is mediated by a family of glycoproteins, the cadherins. Cadherins are single-pass transmembrane proteins principally involved in calcium-dependent cell adhesion. Classical cadherins consist of the extracellular domain, a hydrophobic membrane-spanning domain and the intracellular cytoplasmic domain. The extracellular region has five tandem repeats of about 110 amino acid residues.
Here the crystal structure of the first repeat of the extracellular domain of mouse neural-cadherin (N-cadherin) is presented. The structure reveals a folding topology similar to that of immunoglobulin variable domains, which was not at first predicted from the amino acid sequence. The domain has a seven-stranded beta sheet with the amino and carboxyl termini located at opposite ends of the molecule and calcium ions bound to the loops adjoining individual domains. In the crystal structure, the N-cadherin extracellular domain interface is found to contain a conserved tryptophan side chain that intercalates into a conserved hydrophobic pocket in a partner molecule. This suggests that the interface is also important in vivo in mediating the homophilic association of classical cadherins.
Protein Data Bank (PDB)
Shapiro, L. Fannon, A.M. Kwong, P.D. Thompson, A. Lehmann, M.S. Grubel, G. Legrand, J.F. Als-Nielsen, J. Colman, D.R. Hendrickson, W.A.; "Structural basis of cell-cell adhesion by cadherins."; Nature; (1995) 374:327-337 PubMed:7885471.
author: Aki Nagata