Article Dans Une Revue International Journal of Biological Macromolecules Année : 2025

Harnessing the power of anti-amyloidogenic polyglutamine binding peptide 1: A computational and biophysical approach to antimicrobial prediction

Résumé

In this work, we demonstrate for the first time the antimicrobial activity of poly-Q binding peptide 1 (QBP1), an anti-amyloidogenic molecule previously identified by phage display for its ability to bind and inhibit the aggregation of polyglutamine proteins like Huntingtin, but also α-synuclein and prion models. Intriguingly, sequence analysis by the ADAPTABLE web server highlighted QBP1's potential antifungal and antibacterial activity, which we have now confirmed experimentally. A theoretical basis for the predicted mechanism of action was provided by molecular dynamics simulations revealing the role of QBP1 aggregates promoting membrane disruption and specific interactions between QBP1 and bacterial and fungal phospholipids, further substantiated by solid-state NMR studies. Using primary human cells, we demonstrated that QBP1 does not display toxicity at high concentrations. Finally, our data demonstrate QBP1's efficacy against some strains of Bacillus cereus, B. mojavensis, Staphylococcus aureus, S. epidermidis, Micrococcus luteus, Enterococcus faecalis, Escherichia coli, and Candida. This unexpected dual function of QBP1 opens new avenues for therapeutic development, potentially restoring the putative antimicrobial protection exerted by many amyloidogenic proteins.

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hal-05101765 , version 1 (04-07-2025)

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Francisco Ramos-Martín, François Peltier, Saoussen Oueslati, Liam Cousin, Mariam Rima, et al.. Harnessing the power of anti-amyloidogenic polyglutamine binding peptide 1: A computational and biophysical approach to antimicrobial prediction. International Journal of Biological Macromolecules, 2025, 318 (Partie 1), pp.144938. ⟨10.1016/j.ijbiomac.2025.144938⟩. ⟨hal-05101765⟩
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