Binding of the elastin peptide VGVAPG and lactose to the human elastin binding protein.

Fiche publication

Date publication

mars 2026

Journal

Journal of structural biology

Auteurs

Membres identifiés du Cancéropôle Est :
Pr DAUCHEZ Manuel , Pr DEBELLE Laurent , Pr BAUD Stéphanie

Tous les auteurs :
Haslak ZP, Belloy N, Debelle L, Dauchez M, Baud S

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/41895457

Résumé

Elastin-derived peptides (EDPs) interact with elastin-binding protein (EBP), a key component of the elastin receptor complex, modulating cellular processes such as protease activation, apoptosis, and chemotaxis via regulation of NEU-1 sialidase activity. Despite their therapeutic relevance, the structural basis of EDP-EBP interactions remains poorly understood. Here, we present the first full-length homology model of EBP (residues 29-516), constructed and validated through duplicate 1 microsecond long molecular dynamics (MD) simulations. Molecular docking of VGVAPG (as a representative EDP) and lactose (as a representative galactosugar) followed by MD simulations, allowed us to identify key binding residues: D98, E99, S104, and S136 for VGVAPG; and E99, S101, S104, N116, Q124, E137, and Y139 for lactose. These data reveal a shared binding region within residues 83-139, suggesting a competitive binding between EDPs and galactosugars. Furthermore, EBP residues P233 and I234 were implicated in potential interactions with PPCA or NEU-1, contributing to ERC assembly. These findings offer new insights into the molecular recognition mechanisms of EBP and provide a foundation for the design of EBP-targeted elastin peptide antagonists.