Side chain interactions govern the response of polypeptide alpha-helices under mechanical stress and prevent the formation of beta-sheets - Archive ouverte HAL Accéder directement au contenu
Pré-Publication, Document De Travail Année : 2022

Side chain interactions govern the response of polypeptide alpha-helices under mechanical stress and prevent the formation of beta-sheets

Marie Asano
  • Fonction : Auteur
Damien Sluysmans
  • Fonction : Auteur
Nicolas Willet
  • Fonction : Auteur
Sébastien Lecommandoux
Anne-Sophie Duwez

Résumé

Secondary a-helix and b-sheet structures are key scaffolds around which the rest of the residues condense during protein folding. They are crucial for proteins to adopt their correct native structure. Despite their key role in numerous processes to maintain life, little is known about their properties under force. Their stability under mechanical stress, as constantly experienced in the turbulent environment of cells, is however essential. Here, we designed and synthesized two pH-responsive polypeptides, poly(L-glutamic acid) and poly(L-lysine), for optimal interfacing with an AFM single-molecule force spectroscopy set-up to probe the mechanical unfolding of a-helix and b-sheet secondary motifs. The force experiments, supported by simulations, reveal a superior mechanical stability of the poly(L-Lysine) a-helix, which we attribute to hydrophobic interactions of the alkyl side chains. Most importantly, our results show that these interactions play a key role in inhibiting the formation of a metastable b-sheet-like structure when the polypeptide is subjected to mechanical deformations, which might have important implications in the mechanism behind polyQ diseases.

Domaines

Chimie
Fichier principal
Vignette du fichier
side-chain-interactions-govern-the-response-of-polypeptide-alpha-helices-under-mechanical-stress-and-prevent-the-formation-of-beta-sheets.pdf (6.5 Mo) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)

Dates et versions

hal-03874315 , version 1 (29-11-2022)

Identifiants

Citer

Marie Asano, Damien Sluysmans, Nicolas Willet, Colin Bonduelle, Sébastien Lecommandoux, et al.. Side chain interactions govern the response of polypeptide alpha-helices under mechanical stress and prevent the formation of beta-sheets. 2022. ⟨hal-03874315⟩
55 Consultations
10 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More