title: A soluble VE-cadherin fragment forms 2D arrays of dimers upon binding to a lipid monolayer.
abstract: A high concentration of cadherin molecules at cell-cell adhesion sites is believed to be essential for generating strong intercellular junctions. In order to determine the interactions of cadherin domains involved in the early stages of lateral cluster formation on the cell surface, a recombinant fragment encompassing the first four domains of human VE-cadherin with a His-tag at the C terminus (VE-EC1-4-His) was produced. Two-dimensional crystals of VE-EC1-4-His were formed at the air-water interface using conventional lipids modified to contain a Ni(2+)-chelating group, which provides a specific site for interaction with the polyhistidine tag. The VE-EC1-4-His was monomeric at the concentration employed for crystal formation; however, the crystals exhibited a p2 symmetry and the presence of cis-dimer interactions between symmetry-related molecules. The VE-EC1-4-His molecules in the crystalline array have a remarkably compact conformation in contrast to the elongated "string of pearls" conformation seen in the hexameric assembly of VE-EC1-4-His in solution, and as seen in the crystal structure of C-cadherin. These results indicate that VE-cadherin can exist in at least two oligomeric states with different interactions between domains and can adopt highly different conformational states. We suggest that the compact cis-dimeric state may occur on isolated cells and that the compact form may serve to protect the molecule from degradation. As previously proposed we suppose that the trans-hexameric form is involved in intercellular adhesion.
authors.affiliation: LIM Institut de Biologie Structurale Jean-Pierre Ebel (CEA-CNRS-Université J. Fourier), 41 rue Jules Horowitz, 38027 Grenoble Cedex 1, France.
authors.forename: Rana
authors.initials: R
authors.lastname: Al-Kurdi
authors.forename: Danielle
authors.initials: D
authors.lastname: Gulino-Debrac
authors.forename: Laurence
authors.initials: L
authors.lastname: Martel
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Legrand
authors.forename: Anne
authors.initials: A
authors.lastname: Renault
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hewat
authors.forename: Catherine
authors.initials: C
authors.lastname: Vénien-Bryan
mesh_terms: D015703:Antigens, CD; D015820:Cadherins / Q000378:metabolism* / Q000648:ultrastructure; D002850:Chromatography, Gel; D019281:Dimerization; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism; D008854:Microscopy, Electron; D010455:Peptides / Q000378:metabolism*; D015202:Protein Engineering; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D010455:Peptides; D000099152:Cadherin 5