Exploring the Nature of Desmosomal Cadherin Associations in 3D
Figure 2
Type I or classical cadherin structure obtained from X-ray crystallographic studies. Structurally the extracellular portion of the cadherin molecule (also known as ectodomains and abbreviated EC) appears as five tandem Ig-like domains, each domain adopting a β-sandwich fold with the topology of a Greek key. Between each domain reside three calcium ions (green spheres) conferring rigidity to the domain interface and inducing the entire structure to assume an extended curve with a defined tilt of ~100° between the long axes of EC1, and 5. Disulfide bonds, O-linked sugars, and N-linked sugars are represented in cyan, red, and blue, respectively (a). In classical cadherins a conserved tryptophan residue near the N-terminus of EC1 has been shown to be crucial in the process of adhesion and is also conserved in desmosomal cadherins (abbreviated to Trp2 and is depicted in purple by space filling representation in both a, and b. This Trp2 is visibly protruding from the cadherin molecule when viewed at rotation from a (b)) The tip-to-tip associations between the EC1 domains of cadherin molecules from opposing cells membranes form the strand dimer interface (c and at rotation in d). EC1 domain binding interaction between opposing cadherins is highlighted in the magnified view (e). The side chain of Trp2 has been suggested as a possible binding site within a hydrophobic pocket in EC1 of a corresponding partner cadherin from the opposing cell membrane. Trp2 side chains (displayed as a backbone worm trace) can be seen inserting into a large concave cavity (depicted as grey shading in the molecular surface model) of the opposing EC1 domain (f). As the Trp2 is conserved in desmosomal cadherins it is assumed that the Trp2 interaction from classical cadherin studies is a compelling model for desmosomal cadherin association, forming a symmetric interdigitation interaction between cadherins of opposing cell membranes, and is known as the strand dimer model (g). Cadherin ectodomains from opposing cells are represented by blue or pink colors. Trp2 side chains (space filling representation) are depicted in the color representing the cell. Yellow represents disulfide bonds. Modified from [50] reprinted with permission from AAAS.
