Interaction of the chaperones alpha B-crystallin and CHIP with fibrillar alpha-synuclein: Effects on internalization by cells and identification of interacting interfaces.

Date publication

juin 2020

Journal

Biochemical and biophysical research communications

Auteurs

Membres identifiés du Cancéropôle Est :
Dr MONSELLIER Elodie

Tous les auteurs :
Bendifallah M, Redeker V, Monsellier E, Bousset L, Bellande T, Melki R

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/32430178

Résumé

The spread of fibrillar alpha-synuclein from affected to naïve neuronal cells is thought to contribute to the progression of synucleinopathies. The binding of fibrillar alpha-synuclein to the plasma membrane is key in this process. We and others previously showed that coating fibrillar alpha-synuclein by the molecular chaperone Hsc70 affects fibrils properties. Here we assessed the effect of the two molecular chaperones alpha B-crystallin and CHIP on alpha-synuclein fibrils uptake by Neuro-2a cells. We demonstrate that both chaperones diminish fibrils take up by cells. We identify through a cross-linking and mass spectrometry strategy the interaction interfaces between alpha-synuclein fibrils and alpha B-crystallin or CHIP. Our results open the way for designing chaperone-derived polypeptide binders that interfere with the propagation of pathogenic alpha-synuclein assemblies.

Mots clés

Cross linking, mass spectrometry, Molecular chaperones, Protein-protein interactions, Protein-protein interfaces

Référence

Biochem Biophys Res Commun. 2020 06 30;527(3):760-769