Dataset Information

Interaction between the elastin peptide VGVAPG and human elastin binding protein.

ABSTRACT: The elastin binding protein (EBP), a spliced variant of lysosomal ?-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.

SUBMITTER: Blanchevoye C

PROVIDER: S-EPMC3543015 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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Interaction between the elastin peptide VGVAPG and human elastin binding protein.

Blanchevoye Charlotte C Floquet Nicolas N Scandolera Amandine A Baud Stéphanie S Maurice Pascal P Bocquet Olivier O Blaise Sébastien S Ghoneim Christelle C Cantarelli Benoît B Delacoux Frédéric F Dauchez Manuel M Efremov Roman G RG Martiny Laurent L Duca Laurent L Debelle Laurent L

The Journal of biological chemistry 20121119 2

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 mo ...[more]

PMID: 23166321

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Project description:Protein-protein interactions play an essential role in cellular processes. Certain proteins form stable complexes with their partner proteins, whereas others function by forming transient complexes. The conventional protein-protein interaction model describes an interaction between two proteins under the assumption that a protein binds to its partner protein through a single binding site. In this study, we improved the conventional interaction model by developing a Multiple-Site (MS) model in which a protein binds to its partner protein through closely located multiple binding sites on a surface of the partner protein by transiently docking at each binding site with individual binding free energies. To test this model, we used the protein-protein interaction mediated by Src homology 3 (SH3) domains. SH3 domains recognize their partners via a weak, transient interaction and are therefore promiscuous in nature. Because the MS model requires large amounts of data compared with the conventional interaction model, we used experimental data from the positionally addressable syntheses of peptides on cellulose membranes (SPOT-synthesis) technique. From the analysis of the experimental data, individual binding free energies for each binding site of peptides were extracted. A comparison of the individual binding free energies from the analysis with those from atomistic force fields gave a correlation coefficient of 0.66. Furthermore, application of the MS model to 10 SH3 domains lowers the prediction error by up to 9% compared with the conventional interaction model. This improvement in prediction originates from a more realistic description of complex formation than the conventional interaction model. The results suggested that, in many cases, SH3 domains increased the protein complex population through multiple binding sites of their partner proteins. Our study indicates that the consideration of general complex formation is important for the accurate description of protein complex formation, and especially for those of weak or transient protein complexes.

Dataset Information

Interaction between the elastin peptide VGVAPG and human elastin binding protein.

Publications

Interaction between the elastin peptide VGVAPG and human elastin binding protein.

Similar Datasets

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