Fig. 9: Modeling of CCC clusters.

a Structural representation of an isolated CCC. Left: The side view of CCC. It displays the cadherin extracellular region (ectodomain), depicted by five ellipsoids corresponding to cadherin extracellular domains, plasma membrane region (PM), and intracellular cadherin tail in complex with catenins (cadherin tail+catenins). Two CCC domains playing critical roles in adhesion are specified: (i) The amino-terminal domain (EC1). Its key adhesion interface residue, W2, is indicated by red dot; (ii) the actin-binding domain of α-catenin, αABD, and the flexible linker separating it from the rest of CCC (αABD+ linker, both shown in red). Right: A vertical projection of the cadherin ectodomain and αABD bound to actin. The ectodomain is depicted as an arrow, its pointed end corresponds to the EC1 domain. The red dot represents the W2 residue. b Types of inter-CCC interactions. Three types of interactions between CCCs have been identified: two modes of interactions are known for the ectodomain, cis-binding (cis) and trans-binding (trans, the ectodomains colored in gray and green belong to two adjacent cells). Note that trans-interacting ectodomains are perpendicular to each other. Inside the cells CCCs interact in cis through αABD-actin interactions (αABD-actin). c Types of CCC oligomers. The inter-CCC interactions spontaneously produce two types of oligomers: (i) At sites of cell-cell contacts, cis and trans interactions of the ectodomain form E-clusters (reviewed in refs. ^2,3,72). (ii) Predominantly at cell protrusions, the αABD-actin interactions generate CCC/actin strands (this study). d Intermix of two oligomers. Both oligomerization processes could be intermixed forming a composite CCC oligomer (E/actin cluster). The size of the E/actin clusters is apparently variable and could incorporate different number of CCC/actin strands.