Titre :

NMR-identification of the interaction between BRCA1 and the intrinsically disordered monomer of the Myc-associated factor X.

Auteur(s) :

Epasto, L. M. [Auteur]
Pötzl, C. [Auteur]
Peterlik, H. [Auteur]
Khalil, Mahdi [Auteur]
Laboratoire Avancé de Spectroscopie pour les Intéractions la Réactivité et l'Environnement - UMR 8516 [LASIRE]
Saint-Pierre, C. [Auteur]
Université Grenoble Alpes [UGA]
Gasparutto, D. [Auteur]
Sicoli, Giuseppe [Auteur]
Laboratoire Avancé de Spectroscopie pour les Intéractions la Réactivité et l'Environnement (LASIRE) - UMR 8516
Kurzbach, D. [Auteur]

Titre de la revue :

Protein Science

Nom court de la revue :

Protein Sci

Pagination :

e4849

Date de publication :

2023-12-09

ISSN :

1469-896X

Mot(s)-clé(s) en anglais :

complexation
MAX
NMR
RCA1

Discipline(s) HAL :

Chimie/Chimie théorique et/ou physique

Résumé en anglais : [en]

The breast cancer susceptibility 1 (BRCA1) protein plays a pivotal role in modu-lating the transcriptional activity of the vital intrinsically disordered transcrip-tion factor MYC. In this regard, mutations of BRCA1 and ...
Lire la suite >The breast cancer susceptibility 1 (BRCA1) protein plays a pivotal role in modu-lating the transcriptional activity of the vital intrinsically disordered transcrip-tion factor MYC. In this regard, mutations of BRCA1 and interruption of itsregulatory activity are related to hereditary breast and ovarian cancer (HBOC).Interestingly, so far, MYC's main dimerization partner MAX (MYC-associatedfactor X) has not been found to bind BRCA1 despite a high sequence similaritybetween both oncoproteins. Herein, we show that a potential reason for this dis-crepancy is the heterogeneous conformational space of MAX, which encloses awell-documented folded coiled-coil homodimer as well as a less common intrin-sically disordered monomer state—contrary to MYC, which exists mostly asintrinsically disordered protein in the absence of any binding partner. We showthat when the intrinsically disordered state of MAX is artificially overpopulated,the binding of MAX to BRCA1 can readily be observed. We characterize thisinteraction by nuclear magnetic resonance (NMR) spectroscopy chemical shiftand relaxation measurements, complemented with ITC and SAXS data. Ourresults suggest that BRCA1 directly binds the MAX monomer to form a disor-dered complex. Though probed herein under biomimetic in-vitro conditions,this finding can potentially stimulate new perspectives on the regulatory net-work around BRCA1 and its involvement in MYC:MAX regulationLire moins >

Langue :

Anglais

Comité de lecture :

Oui

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

Université de Lille
CNRS

Collections :

• Laboratoire Avancé de Spectroscopie pour les Intéractions la Réactivité et l'Environnement (LASIRE) - UMR 8516

Date de dépôt :

2024-02-28T22:05:25Z
2024-03-11T12:22:51Z