Titre :

Regulation of the interaction between the neuronal BIN1 isoform 1 and Tau proteins - role of the SH3 domain

Auteur(s) :

Malki, Idir [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Cantrelle, Francois-Xavier [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Sottejeau, Yoann [Auteur]
Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 [RID-AGE]
Lippens, Guy [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Lambert, Jean-Charles [Auteur]
Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 [RID-AGE]
Landrieu, Isabelle [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]

Titre de la revue :

The FEBS Journal

Numéro :

284

Pagination :

3218-3229

Date de publication :

2017-10

ISSN :

1742464X

Mot(s)-clé(s) en anglais :

Alzheimer’s disease
BIN1
nuclearmagnetic resonance spectroscopy
protein–protein interaction
SH3 domain
Tau

Discipline(s) HAL :

Chimie/Chimie théorique et/ou physique

Résumé en anglais : [en]

Bridging integrator 1 (bin1) gene is a genetic determinant of Alzheimer's disease (AD) and has been reported to modulate Alzheimer's pathogenesis through pathway(s) involving Tau. The functional impact of Tau/BIN1 interaction ...
Lire la suite >Bridging integrator 1 (bin1) gene is a genetic determinant of Alzheimer's disease (AD) and has been reported to modulate Alzheimer's pathogenesis through pathway(s) involving Tau. The functional impact of Tau/BIN1 interaction as well as the molecular details of this interaction are still not fully resolved. As a consequence, how BIN1 through its interaction with Tau affects AD risk is also still not determined. To progress in this understanding, interaction of Tau with two BIN1 isoforms was investigated using Nuclear Magnetic Resonance spectroscopy. 1H, 15N spectra showed that the C‐terminal SH3 domain of BIN1 isoform 1 (BIN1Iso1) is not mobile in solution but locked with the core of the protein. In contrast, the SH3 domain of BIN1 isoform 9 (BIN1Iso9) behaves as an independent mobile domain. This reveals an equilibrium between close and open conformations for the SH3 domain. Interestingly, a 334–376 peptide from the clathrin and AP‐2‐binding domain (CLAP) domain of BIN1Iso1, which contains a SH3‐binding site, is able to compete with BIN1‐SH3 intramolecular interaction. For both BIN1 isoforms, the SH3 domain can interact with Tau(210–240) sequence. Tau(210–240) peptide can indeed displace the intramolecular interaction of the BIN1‐SH3 of BIN1Iso1 and form a complex with the released domain. The measured Kd were in agreement with a stronger affinity of Tau peptide. Both CLAP and Tau peptides occupied the same surface on the BIN1‐SH3 domain, showing that their interaction is mutually exclusive. These results emphasize an additional level of complexity in the regulation of the interaction between BIN1 and Tau dependent of the BIN1 isoforms.Lire moins >

Langue :

Anglais

Audience :

Non spécifiée

Établissement(s) :

CNRS
Université de Lille

Collections :

• Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576

Équipe(s) de recherche :

RMN et interactions moléculaires

Date de dépôt :

2020-02-12T15:44:49Z
2021-02-26T10:05:26Z
2021-05-20T15:34:48Z