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.
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Authors | Charlotte Blanchevoye, Nicolas Floquet, Amandine Scandolera, Stéphanie Baud, Pascal Maurice, Olivier Bocquet, Sébastien Blaise, Christelle Ghoneim, Benoît Cantarelli, Frédéric Delacoux, Manuel Dauchez, Roman G Efremov, Laurent Martiny, Laurent Duca, Laurent Debelle |
Journal | The Journal of biological chemistry
(J Biol Chem)
Vol. 288
Issue 2
Pg. 1317-28
(Jan 11 2013)
ISSN: 1083-351X [Electronic] United States |
PMID | 23166321
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Validation Study)
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Chemical References |
- DNA Primers
- Oligopeptides
- Receptors, Cell Surface
- elastin-binding proteins
- Elastin
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Topics |
- Amino Acid Sequence
- Animals
- Base Sequence
- Binding Sites
- COS Cells
- Chlorocebus aethiops
- DNA Primers
- Elastin
(chemistry, metabolism)
- Humans
- Models, Molecular
- Molecular Docking Simulation
- Mutagenesis, Site-Directed
- Oligopeptides
(metabolism)
- Protein Binding
- Receptors, Cell Surface
(chemistry, genetics, metabolism)
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