Solution structures of the adhesion molecule DdCAD-1 reveal new insights into Ca(2+)-dependent cell-cell adhesion

Nat Struct Mol Biol. 2006 Nov;13(11):1016-22. doi: 10.1038/nsmb1162. Epub 2006 Oct 22.


DdCAD-1 is a novel Ca(2+)-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 Ca(2+)-free and Ca(2+)-bound monomeric DdCAD-1. DdCAD-1 contains two beta-sandwich domains, belonging to the betagamma-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 Ca(2+)-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 Ca(2+)-dependent mechanisms for cell-cell adhesion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Calcium / metabolism*
  • Cell Adhesion Molecules / chemistry*
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism*
  • Cell Adhesion*
  • Cell Membrane / metabolism
  • Dictyostelium / chemistry
  • Dictyostelium / cytology*
  • Dictyostelium / genetics
  • Dictyostelium / metabolism
  • Dimerization
  • Models, Molecular
  • Nuclear Magnetic Resonance, Biomolecular
  • Protein Binding
  • Protein Structure, Tertiary


  • Cell Adhesion Molecules
  • Calcium

Associated data

  • PDB/1YHP
  • PDB/2B1O