Titre :

Site-Specific Incorporation of Fluorinated Prolines into Proteins and their Impact on Neighbouring Residues

Auteur(s) :

Elena-Real, Carlos [Auteur]
Centre de Biologie Structurale [Montpellier] [CBS]
Urbanek, Annika [Auteur]
Centre de Biologie Structurale [Montpellier] [CBS]
Sagar, Amin [Auteur]
Centre de Biologie Structurale [Montpellier] [CBS]
Mohanty, Priyesh [Auteur]
Levy, Geraldine [Auteur]
Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 [RID-AGE]
Biologie Structurale Intégrative [ERL 9002 - INSERM U1167 - BSI]
Morató, Anna [Auteur]
Centre de Biologie Structurale [Montpellier] [CBS]
Fournet, Aurélie [Auteur]
Centre de Biologie Structurale [Montpellier] [CBS]
Allemand, Frédéric [Auteur]
Centre de Biologie Structurale [Montpellier] [CBS]
Sibille, Nathalie [Auteur]
Centre de Biologie Structurale [Montpellier] [CBS]
Mittal, Jeetain [Auteur]
Sinnaeve, Davy [Auteur]
Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 [RID-AGE]
Biologie Structurale Intégrative [ERL 9002 - INSERM U1167 - BSI]
Bernadó, Pau [Auteur]
Centre de Biologie Structurale [Montpellier] [CBS]

Titre de la revue :

Chemistry - a European Journal

Éditeur :

Wiley-VCH Verlag

Date de publication :

2025

ISSN :

0947-6539

Mot(s)-clé(s) en anglais :

Huntingtin
Fluorinated amino acids
NMR Spectroscopy
Non-canonical amino acids

Discipline(s) HAL :

Sciences du Vivant [q-bio]/Biochimie, Biologie Moléculaire/Biologie structurale [q-bio.BM]
Chimie/Chimie théorique et/ou physique

Résumé en anglais : [en]

The incorporation of fluorinated amino acids into proteins provides new opportunities to study biomolecular structure-function relationships in an elegant manner. The available strategies to incorporate the majority of ...
Lire la suite >The incorporation of fluorinated amino acids into proteins provides new opportunities to study biomolecular structure-function relationships in an elegant manner. The available strategies to incorporate the majority of fluorinated amino acids are not site-specific or imply important structural modifications. Here, we present a chemical biology approach for the site-specific incorporation of three commercially available Cγ-modified fluoroprolines that has been validated using a non-pathogenic version of huntingtin exon-1 (HttExon-1). 19F, 1H and 15N NMR chemical shifts measured for multiple variants of HttExon-1 indicated that the trans/cis ratio was strongly dependent on the fluoroproline variant and the sequence context. By isotopically labelling the rest of the protein, we have shown that the extent of spectroscopic perturbations to the neighbouring residues depends on the number of fluorine atoms and the stereochemistry at Cγ, as well as the isomeric form of the fluoroproline. We have rationalized these observations by means of extensive molecular dynamics simulations, indicating that the observed atomic chemical shift perturbations correlate with the distance to fluorine atoms and that the effect remains very local. These results validate the site-specific incorporation of fluoroprolines as an excellent strategy to monitor intra- and intermolecular interactions in disordered proline-rich proteins.Lire moins >

Langue :

Anglais

Comité de lecture :

Oui

Audience :

Internationale

Vulgarisation :

Non

Projet Européen :

Structure and Dynamics of Low-Complexity Regions in Proteins: The Huntingtin Case

Collections :

• Facteurs de risque et déterminants moléculaires des maladies liées au vieillissement (RID-AGE) - U1167

Source :

Harvested from HAL

Date de dépôt :

2025-01-24T08:09:31Z