title: Interaction between the elastin peptide VGVAPG and human elastin binding protein.
abstract: The elastin binding protein (EBP), a spliced variant of lysosomal β-galactosidase, is the primary receptor of elastin peptides that have been linked to emphysema, aneurysm and cancer progression. The sequences recognized by EBP share the XGXXPG consensus pattern found in numerous matrix proteins, notably in elastin where the VGVAPG motif is repeated. To delineate the elastin binding site of human EBP, we built a homology model of this protein and docked VGVAPG on its surface. Analysis of this model suggested that Gln-97 and Asp-98 were required for interaction with VGVAPG because they contribute to the definition of a pocket thought to represent the elastin binding site of EBP. Additionally, we proposed that Leu-103, Arg-107, and Glu-137 were essential residues because they could interact with VGVAPG itself. Site-directed mutagenesis experiments at these key positions validated our model. This work therefore provides the first structural data concerning the interaction of the VGVAPG with its cognate receptor. The present structural data should now allow the development of EBP-specific antagonists.
authors.affiliation: Laboratoire de Signalisation et Récepteurs Matriciels, FRE CNRS 3184, Université de Reims Champagne Ardenne, UFR Sciences Exactes et Naturelles, Moulin de la Housse, BP 1039, 51687 Reims Cedex 2, France.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Blanchevoye
authors.forename: Nicolas
authors.initials: N
authors.lastname: Floquet
authors.forename: Amandine
authors.initials: A
authors.lastname: Scandolera
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Baud
authors.forename: Pascal
authors.initials: P
authors.lastname: Maurice
authors.forename: Olivier
authors.initials: O
authors.lastname: Bocquet
authors.forename: Sébastien
authors.initials: S
authors.lastname: Blaise
authors.forename: Christelle
authors.initials: C
authors.lastname: Ghoneim
authors.forename: Benoît
authors.initials: B
authors.lastname: Cantarelli
authors.forename: Frédéric
authors.initials: F
authors.lastname: Delacoux
authors.forename: Manuel
authors.initials: M
authors.lastname: Dauchez
authors.forename: Roman G
authors.initials: RG
authors.lastname: Efremov
authors.forename: Laurent
authors.initials: L
authors.lastname: Martiny
authors.forename: Laurent
authors.initials: L
authors.lastname: Duca
authors.forename: Laurent
authors.initials: L
authors.lastname: Debelle
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D019556:COS Cells; D002522:Chlorocebus aethiops; D017931:DNA Primers; D004549:Elastin / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D016297:Mutagenesis, Site-Directed; D009842:Oligopeptides / Q000378:metabolism*; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D009842:Oligopeptides; D011956:Receptors, Cell Surface; C054901:elastin-binding proteins; D004549:Elastin