Type II Cadherin Ectodomain Structures: Implications for Classical Cadherin Specificity

Abstract

Type I and II classical cadherins help to determine the adhesive specificities of animal cells. Crystal-structure determination of ectodomain regions from three type II cadherins reveals adhesive dimers formed by exchange of N-terminal beta strands between partner extracellular cadherin-1 (EC1) domains. These interfaces have two conserved tryptophan side chains that anchor each swapped strand, compared with one in type I cadherins, and include large hydrophobic regions unique to type II interfaces. The EC1 domains of type I and type II cadherins appear to encode cell adhesive specificity in vitro. Moreover, perturbation of motor neuron segregation with chimeric cadherins depends on EC1 domain identity, suggesting that this region, which includes the structurally defined adhesive interface, encodes type II cadherin functional specificity in vivo.

Sequence and Structural Determinants of Strand Swapping in Cadherin Domains: Do All Cadherins Bind Through the Same Adhesive Interface?

“…The three-dimensional structures of a number of type I and type II cadherin ectodomain adhesive regions have been determined by both X-ray crystallography and NMR, and the structure for the full ectodomain of Xenopus laevis C-cadherin has also been determined [13][14][15][16][17][18][19][20][21][22][23] . Table 1 contains a list of all available cadherin structures 13-25 .…”

“…discussion in Patel et al, 2006). For example, a variety of mutations that disrupt the swapped interface have been shown to abrogate adhesion in cell aggregation studies 26-29 . Moreover, electron tomography studies of desmosomes 30 suggest that the EC1-EC1 interface seen in the crystal structure of C-cadherin 17 is indistinguishable at the resolution of these studies from the interface formed between trans cadherin dimers located on apposing cell surfaces.…”

Depletion of E-Cadherin Disrupts Establishment but Not Maintenance of Cell Junctions in Madin-Darby Canine Kidney Epithelial Cells

“…The extracellular domain is composed of five ectodomain modules (ECs), with the most membranedistal module (EC1) mediating binding with the E-cadherin on the adjacent cell (Boggon et al, 2002). Calcium ions bind between the EC domains to promote a rod-like conformation required for transinteractions (Gumbiner, 1996;Patel et al, 2006). The cytoplasmic tail of E-cadherin binds to the armadillo repeat protein ␤-catenin, an important target of the Wnt signaling pathway and a cofactor for TCF/LEF-mediated transcription (Gavard and Mege, 2005).…”

Expression of the extracellular domain of OB-cadherin as an Fc fusion protein using bicistronic retroviral expression vector

“…A report by Patel et al [8] described the expression of the first domain of mouse OB-cadherin protein, i.e., amino acids 1-98, in E. coli, for crystalstructure determination. They showed that the protein assumed a dimeric conformation similar to E-cadherin and proposed that the first domain of OB-cadherin is the adhesion domain.…”

“…OBcadherin, like other classical cadherins, is composed of an extracellular domain with five repeated subdomains (EC 1-5), a single transmembrane domain, and a cytoplasmic C-terminal tail [5]. The calcium binding sites are located in the extracellular domain and participate in the homodimerization of cadherin present on neighboring cells [8][9][10][11]. Expression of OB-cadherin is associated with osteoblast differentiation and has been proposed to function in cell sorting, migration, and alignment during the maturation of osteoblasts [12].…”