Solution structures of the adhesion molecule DdCAD-1 reveal new insights into Ca2+-dependent cell-cell adhesion

Abstract

DdCAD-1 is a novel Ca2+-dependent cell adhesion molecule that lacks a hydrophobic signal peptide and a transmembrane domain. DdCAD-1 is expressed by the social amoeba Dictyostelium discoideum at the onset of development. It is synthesized as a soluble protein and then transported to the plasma membrane by contractile vacuoles. Here we describe the novel features of the solution structures of Ca2+-free and Ca2+-bound monomeric DdCAD-1. DdCAD-1 contains two β-sandwich domains, belonging to the βγ-crystallin and immunoglobulin fold classes, respectively. Whereas the N-terminal domain has a major role in homophilic binding, the C-terminal domain tethers the protein to the cell membrane. From structural and mutational analyses, we propose a model for the Ca2+-bound DdCAD-1 dimer as a basis for understanding DdCAD-1-mediated cell-cell adhesion at the molecular level. Our results provide new insights into Ca2+-dependent mechanisms for cell-cell adhesion. © 2006 Nature Publishing Group.