PMID: 21269602

 

    Legend: Sugar

Title : Structure and binding mechanism of vascular endothelial cadherin : a divergent classical cadherin

Abstract :

1. Vascular endothelial cadherin (VE-cadherin ), a divergent member of the type II classical cadherin family of cell adhesion proteins , mediates homophilic adhesion in the vascular endothelium
2. Previous investigations with a bacterially produced protein suggested that VE-cadherin forms cell surface trimers that bind between apposed cells to form hexamers
3. Here we report studies of mammalian-produced VE-cadherin ectodomains suggesting that, like other classical cadherins, VE-cadherin forms adhesive trans dimers between monomers located on opposing cell surfaces
4. Trimerization of the bacterially produced protein appears to be an artifact that arises from a lack of glycosylation
5. We also present the 2.1-Å-resolution crystal structure of the VE-cadherin EC1-2 adhesive region , which reveals homodimerization via the strand-swap mechanism common to classical cadherins
6. In common with type II cadherins, strand-swap binding involves two tryptophan anchor residues , but the adhesive interface resembles type I cadherins in that VE-cadherin does not form a large nonswapped hydrophobic surface
7. Thus, VE-cadherin is an outlier among classical cadherins, with characteristics of both type I and type II subfamilies