title: Synergy between extracellular modules of vascular endothelial cadherin promotes homotypic hexameric interactions.
abstract: Vascular endothelial (VE) cadherin is an endothelial specific cadherin that plays a major role in remodeling and maturation of vascular vessels. Recently, we presented evidence that the extracellular part of VE cadherin, which consists of five homologous modules, associates as a Ca(2+)-dependent hexamer in solution (Legrand, P., Bibert, S., Jaquinod, M., Ebel, C., Hewat, E., Vincent, F., Vanbelle, C., Concord, E., Vernet, T., and Gulino, D. (2001) J. Biol. Chem. 276, 3581-3588). In an effort to identify which extracellular modules are involved in the elaboration and stability of this hexameric structure, we expressed various VE cadherin-derived fragments overlapping individual or multiple successive modules as soluble proteins, purified each to homogeneity, and tested their propensity to self-associate. Altogether, the results demonstrate that, as their length increases, VE cadherin recombinant fragments generate increasingly complex self-associating structures; although single module fragments do not oligomerize, some two or three module-containing fragments self-assemble as dimers, and four module-containing fragments associate as hexamers. Our results also suggest that, before elaborating a hexameric structure, molecules of VE cadherin self-assemble as intermediate dimers. A synergy between the extracellular modules of VE cadherin is thus required to build homotypic interactions. Placed in a cellular context, this particular self-association mode may reflect the distinctive biological requirements imposed on VE cadherin at adherens junctions in the vascular endothelium.
authors.affiliation: Laboratoire d'Ingénierie des Macromolécules, Institut de Biologie Structurale Jean-Pierre Ebel, CEA/CNRS, Université Joseph Fourier, 41 Rue Jules Horowitz, 38027 Grenoble Cedex, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Bibert
authors.forename: Michel
authors.initials: M
authors.lastname: Jaquinod
authors.forename: Evelyne
authors.initials: E
authors.lastname: Concord
authors.forename: Christine
authors.initials: C
authors.lastname: Ebel
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hewat
authors.forename: Christophe
authors.initials: C
authors.lastname: Vanbelle
authors.forename: Pierre
authors.initials: P
authors.lastname: Legrand
authors.forename: Marianne
authors.initials: M
authors.lastname: Weidenhaupt
authors.forename: Thierry
authors.initials: T
authors.lastname: Vernet
authors.forename: Danielle
authors.initials: D
authors.lastname: Gulino-Debrac
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D001704:Biopolymers; D015820:Cadherins / Q000737:chemistry / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002850:Chromatography, Gel; D017931:DNA Primers; D004730:Endothelium, Vascular / Q000378:metabolism*; D017510:Protein Folding; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D001704:Biopolymers; D015820:Cadherins; D017931:DNA Primers; D011994:Recombinant Proteins; D002118:Calcium