title: Solution structures of the adhesion molecule DdCAD-1 reveal new insights into Ca(2+)-dependent cell-cell adhesion.
abstract: 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.
authors.affiliation: Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, Singapore 117543.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Lin
authors.forename: Shrivani
authors.initials: S
authors.lastname: Sriskanthadevan
authors.forename: Haibo
authors.initials: H
authors.lastname: Huang
authors.forename: Chi-Hung
authors.initials: CH
authors.lastname: Siu
authors.forename: Daiwen
authors.initials: D
authors.lastname: Yang
mesh_terms: D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D004023:Dictyostelium / Q000737:chemistry / Q000166:cytology* / Q000235:genetics / Q000378:metabolism; D019281:Dimerization; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D017434:Protein Structure, Tertiary
chemical_list: D015815:Cell Adhesion Molecules; D002118:Calcium